CN101073665A - 淋巴毒素在制备增加化疗药物敏感性的药物中的应用 - Google Patents
淋巴毒素在制备增加化疗药物敏感性的药物中的应用 Download PDFInfo
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Abstract
本发明属蛋白质工程和制药领域,具体涉及淋巴毒素在肿瘤治疗领域的应用。本发明公开了一种淋巴毒素的用途,淋巴毒素作为化疗药物的增敏剂,用于治疗上皮来源的肿瘤。淋巴毒素与化疗药物联合使用,对于上皮来源的肿瘤细胞的杀伤效果具有明显的协同作用,其中与铂类药物的协同作用最为显著。通过联合使用一线化疗药物和淋巴毒素,可以提高疗效或者在保证疗效的前提下降低化疗药物的剂量,从而减轻化疗药物带来的毒副作用,改善病人生活质量。
Description
技术领域
本发明涉及淋巴毒素的新用途,具体涉及淋巴毒素在制备增加化疗药物敏感性的药物中的用途。
背景技术
淋巴毒素a(LTα),也被称为TNFβ,是TNF超家族成员之一,是一类重要的细胞因子。LTα由有活性的淋巴细胞产生,是25KD的分泌型糖蛋白,LT前体含有205个氨基酸残基,其中34个氨基酸残基编码信号肽,成熟的LT有171个氨基酸残基(18kD)(SEQ ID NO:3),没有二硫键,第62位为N-连接的糖基化位点(糖基化对其细胞毒活性是非必要的)。LT的N端1-27氨基酸序列为柔性结构,此区域缺失不影响LT与受体的结合以及引发的细胞毒活性。
LTα的结构和功能与TNF相似,具有相同的受体TNFRI、TNFRII。与TNF相似,LT也显示出明确的抗肿瘤作用。LT体内、体外的抗肿瘤活性与TNF不相上下,但毒性更小,半衰期更长。
美国专利US5474023,报道了LT与盐酸阿霉素、5-FU联合使用,可以改进疗效,减轻化疗药物引起的毒副作用。但对其他的化疗药物和LT是否具有协同作用,以及特定的化疗药物和LT联合使用对何种肿瘤最为有效并没有说明。
化疗是目前肿瘤治疗领域主要的治疗方法之一。多种化疗药物广泛使用于临床,对控制病情发展,延长患者寿命起到积极作用。但多数化疗药物的毒副作用较大,容易产生耐药性,而且只对部分瘤种有效,成为临床使用的限制因素。因此,目前迫切需要能够降低化疗药物的毒副作用,扩大抑瘤谱,克服耐药性的产生的药物和治疗手段。
发明内容
本发明需要解决的技术问题是公开一种淋巴毒素在制备增加化疗药物敏感性的药物中的应用。
本发明的构思是这样的:将目前广泛使用的化疗药物和淋巴毒素联合使用,用来杀伤多种肿瘤细胞株;与单独使用化疗药物比较,筛选和淋巴毒素具有协同作用的化疗药物,同时,筛选对该联合治疗最敏感的肿瘤种类。
本发明的目的是提供一种淋巴毒素的用途,用于肿瘤化疗的增敏剂,以解决目前化疗中毒副作用大、病人耐受性差等不足。
本发明筛选的化疗药物包括卡铂、顺铂、奥沙利铂、阿霉素、表阿霉素、5-FU、丝裂霉素、环磷酰胺、长春新碱、长春瑞滨共10种。筛选的肿瘤细胞株包括:BGC-823(胃腺癌)、NCI-H157(非小细胞肺腺癌)、SW480(结肠癌)、SK-BR-3(转移性乳腺腺癌)、A375(黑色素瘤)、Hep2(喉癌)、HeLa(宫颈癌)共7种上皮来源的肿瘤;Raji(非霍奇金淋巴瘤)、Ramos(非霍奇金淋巴瘤)共2种骨髓来源的肿瘤。结果见下表:
淋巴毒素联合化疗药物杀伤肿瘤细胞汇总表
“+”:表示协同作用;“=”:表示叠加作用;“-”:表示拮抗作用
经过广泛深入地研究,发明人发现,淋巴毒素与10种化疗药物联合使用,在2种骨髓来源的肿瘤上均没有协同作用,在某些肿瘤上甚至呈现拮抗作用;然而对于7种上皮来源的肿瘤,淋巴毒素与多种化疗药物呈现明显的协同作用。
发明人还发现,淋巴毒素与铂类化疗药物(顺铂、卡铂、奥沙利铂)、蒽环类药物(阿霉素、表阿霉素)、5-FU、丝裂霉素在治疗上皮来源的肿瘤上具有协同作用,其中与铂类药物的协同作用最为显著。
本发明公开了一种淋巴毒素的用途,淋巴毒素作为化疗药物的增敏剂,用于治疗上皮来源的肿瘤。
所说的淋巴毒素包括来源于人、鼠、猪、马或牛的淋巴毒素,较佳的,选择来源于人的淋巴毒素,更佳的,选择淋巴毒素LT1-171、LT24-171、LT28-171。
所说的上皮来源的肿瘤包括非小细胞肺癌、乳腺癌、喉癌、结直肠癌、子宫颈癌、黑色素瘤或胃癌。
在一个优选的方案中,淋巴毒素可作为铂类药物、蒽环类药物、5-FU、丝裂霉素的增敏剂,用于治疗上皮来源的肿瘤。较佳的,淋巴毒素可作为铂类药物的增敏剂,更佳的,淋巴毒素可作为为卡铂、顺铂、奥沙利铂的增敏剂。
所说的增加上皮来源的肿瘤对化疗药物敏感性的药物指在对患有上皮来源肿瘤患者在化疗前、同时或化疗后给与,以提高患者对化疗药物耐受性或增加化疗药物疗效的药物。
本发明的有益效果体现在:对于上皮来源的肿瘤,包括非小细胞肺癌、胃癌、乳腺癌、宫颈癌等恶性高发肿瘤,通过联合使用一线化疗药物和淋巴毒素,可以提高疗效或者在保证疗效的前提下降低化疗药物的剂量,从而减轻化疗药物带来的毒副作用,改善病人生活质量。
附图说明
图1、rhLT对NCI-H157(非小细胞肺腺癌)细胞的化疗增敏作用
图1.A
CDDP(ug/ml):0.625,1.25,2.5,5;
细胞存活率:87.33%,70.29%,45.29%,16.82%
100ng/LT+CDDP(ug/ml):0.625,1.25,2.5,5;
细胞存活率:62.44%,39.24%,9.53%,9.14%
图1.B
CBDCA(ug/ml):12.5,25,50,100
细胞存活率:86.00%,78.73%,57.98%,36.66%;
100ng/LT+CBDCA(ug/ml):12.5,25,50,100
细胞存活率:68.82%,66.97%,50.20%,24.44%;
图1.C
L-OHP(ug/ml):0.625,1.25,2.5,5
细胞存活率:92.75%,77.17%,63.51%,55.36%;
100ng/LT+L-OHP(ug/ml):0.625,1.25,2.5,5
细胞存活率:71.48%,63.39%,49.97%,45.18%;
图1.D
ADM(ug/ml):0.01171875,0.046875,0.1875,0.75,3
细胞存活率:80.57%,75.95%,48.64%,15.43%,3.55%;
100ng/LT+DM(ug/ml):0.01171875,0.046875,0.1875,0.75,3
细胞存活率:63.53%,60.86%,39.53%,12.17%,2.48%;
图1.E
Epi-ADM(ug/ml):0.0032,0.016,0.08,0.4,2
细胞存活率:94.17%,81.70%,68.27%,31.29%,7.38%;
100ng/LT+Epi-ADM(ug/ml):0.0032,0.016,0.08,0.4,2
细胞存活率:90.34%,70.00%,54.65%,22.80%,5.27%;
图1.F
5-FU(ug/ml):0.00390625,0.015625,0.0625,0.25,1
细胞存活率:71.97%,70.67%,66.76%,60.57%,44.11%;
100ng/LT+5-FU(ug/ml):0.00390625,0.015625,0.0625,0.25,1
细胞存活率:66.60%,65.90%,61.20%,51.57%,30.82%;
图1.G
MMC(ug/ml):0.078125,0.3125,1.25,5,20
细胞存活率:76.78%,73.08%,55.85%,34.05%,9.08%;
100ng/LT+MMC(ug/ml):0.078125,0.3125,1.25,5,20
细胞存活率:95.68%,66.22%,51.50%,28.90%,19.43%;
图1.H
CTX(ug/ml):3.90625,15.625,62.5,250,1000
细胞存活率:70.43%,71.06%,69.43%,65.54%,49.14%;
100ng/LT+CTX(ug/ml):3.90625,15.625,62.5,250,1000
细胞存活率:61.87%,62.09%,56.82%,52.68%,43.71%;
图1.I
VCR(ug/ml):0.00391,0.01563,0.0625,0.25,1
细胞存活率:81.26%,35.34%,22.50%,20.80%,19.43%;
100ng/LT+VCR(ug/ml):0.00391,0.01563,0.0625,0.25,1
细胞存活率:77.82%,27.07%,13.10%,12.36%,12.30%;
图1.J
VNR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:98.13%,97.74%,80.45%,23.42%
100ng/LT+VNR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:91.73%,91.42%,52.55%,12.56%;
图2、rhLT对SK-BR-3(转移性乳腺腺癌)细胞的化疗增敏作用
图2.A
CDDP(ug/ml):0.25,0.5,1.0,2;
细胞存活率:94.53%,88.33%,79.31%,61.53%;
100ng/LT+CDDP(ug/ml):0.25,0.5,1.0,2;
细胞存活率:69.63%,59.77%,46.38%,34.16%;
图2.B
CBDCA(ug/ml):2.5,5.0,10,20;
细胞存活率:98.86%,96.50%,72.35%,60.12%;
100ng/LT+CBDCA(ug/ml):2.5,5.0,10,20;
细胞存活率:50.69%,48.93%,34.29%,21.93%;
图2.C
L-OHP(ug/ml):0.625,1.25,2.5,5
细胞存活率:63.88%,61.78%,52.49%,48.35%;
100ng/LT+L-OHP(ug/ml):0.625,1.25,2.5,5
细胞存活率:49.66%,35.61%,34.44%,29.00%;
图2.D
ADM(ug/ml):0.25,0.5,1.0,2;
细胞存活率:36.07%,23.58%,20.81%,16.26%;
100ng/LT+DM(ug/ml):0.25,0.5,1.0,2;
细胞存活率:31.19%,22.31%,13.65%,11.38%;
图2.E
Epi-ADM(ug/ml):0.015625,0.0625,0.25,1.0
细胞存活率:95.05%,58.56%,44.43%,10.50%;
100ng/LT+Epi-ADM(ug/ml):0.015625,0.0625,0.25,1.0
细胞存活率:69.39%,36.06%,31.51%,5.92%;
图2.F
5-FU(ug/ml):6.25,12.5,25,50;
细胞存活率:57.27%,50.42%,49.26%,45.16%
100ng/LT+5-FU(ug/ml):6.25,12.5,25,50;
细胞存活率:51.89%,45.29%,40.62%,31.90%;
图2.G
MMC(ug/ml):0.03125,0.125,0.5,2;
细胞存活率:101.78%,81.83%,43.05%,20.13%;
100ng/LT+MMC(ug/ml):0.03125,0.125,0.5,2;
细胞存活率:89.73%,53.83%,31.60%,10.33%;
图2.H
CTX(ug/ml):3.90625,15.625,62.5,250,1000
细胞存活率:84.96%,83.67%,82.99%,75.24%,49.31%;
100ng/LT+CTX(ug/ml):3.90625,15.625,62.5,250,1000
细胞存活率:82.48%,77.49%,75.43%,63.64%,45.19%;
图2.I
VCR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:99.22%,98.86%,29.75%,24.63%;
100ng/LT+VCR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:84.94%,78.13%,27.02%,21.25%;
图2.J
VNR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:99.37%,97.05%,32.94%,26.50%;
100ng/LT+VNR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:88.47%,87.24%,28.69%,24.29%;
图3、rhLT对Raji(非霍奇金淋巴瘤)细胞的化疗增敏作用
图3.A
CDDP(ug/ml):0.01953,0.07813,0.3125,1.25,5;
细胞存活率:94.39%,97.21%,85.48%,59.61%,42.30%;
100ng/LT+CDDP(ug/ml):0.01953,0.07813,0.3125,1.25,5;
细胞存活率:95.73%,93.23%,86.30%,66.92%,43.59%;
图3.B
CBDCA(ug/ml):6.25,12.5,25,50;
细胞存活率:98.20%,98.46%,89.13%,66.24%,37.87%;
100ng/LT+CBDCA(ug/ml):6.25,12.5,25,50;
细胞存活率:102.10%,101.97%,97.22%,70.65%,43.09%;
图3.C
L-OHP(ug/ml):0.007813,0.03125,0.125,0.5,2;
细胞存活率:98.64%,96.80%,96.52%,91.29%,51.08%;
100ng/LT+L-OHP(ug/ml):0.007813,0.03125,0.125,0.5,2;
细胞存活率:117.03%,112.19%,108.67%,106.67%,59.83%;
图3.D
ADM(ug/ml):0.01953,0.07813,0.3125,1.25,5;
细胞存活率:92.36%,49.44%,37.19%,16.85%,20.85%;
100ng/LT+DM(ug/ml):0.01953,0.07813,0.3125,1.25,5;
细胞存活率:102.05%,68.07%,47.32%,28.93%,24.57%;
图3.E
Epi-ADM(ug/ml):0.0032,0.016,0.08,0.4,2;
细胞存活率:22.10%,14.52%,11.18%,81.71%,53.98%;
100ng/LT+Epi-ADM(ug/ml):0.0032,0.016,0.08,0.4,2;
细胞存活率:22.02%,23.20%,18.08%,94.58%,62.79%;
图3.F
5-FU(ug/ml):11.71875,46.875,187.5,750,3000;
细胞存活率:82.16%,71.06%,50.58%,52.42%,53.74%;
100ng/LT+5-FU(ug/ml):11.71875,46.875,187.5,750,3000;
细胞存活率:85.57%,74.56%,62.01%,55.60%,59.45%;
图3.G
MMC(ug/ml):0.390625,1.5625,6.25,25,100;
细胞存活率:74.69%,53.10%,37.66%,24.69%,16.45%;
100ng/LT+MMC(ug/ml):0.390625,1.5625,6.25,25,100;
细胞存活率:81.22%,62.14%,37.66%,29.53%,21.56%;
图3.H
CTX(ug/ml):62.5,125,250,500,1000;
细胞存活率:92.08%,86.67%,86.00%,78.04%,63.30%;
100ng/LT+CTX(ug/ml):62.5,125,250,500,1000;
细胞存活率:98.43%,95.56%,88.01%,78.04%,70.13%;
图3.I
VCR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:93.62%,90.76%,88.83%,84.17%;
100ng/LT+VCR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:95.65%,94.32%,90.88%,87.38%;
图3.J
VNR(ug/ml):0.008,0.04,0.2,1,5;
细胞存活率:30.63%,47.09%,25.70%,27.88%,32.55%;
100ng/LT+VNR(ug/ml):0.008,0.04,0.2,1,5;
细胞存活率:32.04%,41.07%,29.54%,46.57%,38.32%;
图4、rhLT对Romos(非霍奇金淋巴瘤)细胞的化疗增敏作用
图4.A
CDDP(ug/ml):0.375,0.75,1.5,3.0;
细胞存活率:95.03%,89.50%,108.42%,142.55%;
100ng/LT+CDDP(ug/ml):0.375,0.75,1.5,3.0;
细胞存活率:156.51%,150.22%,162.85%,195.16%;
图4.B
CBDCA(ug/ml):6.25,12.5,25,50;
细胞存活率:92.51%,93.32%,100.17%,112.30%;
100ng/LT+CBDCA(ug/ml):6.25,12.5,25,50;
细胞存活率:145.10%,133.02%,129.95%,141.67%;
图4.C
L-OHP(ug/ml):0.625,1.25,2.5,5
细胞存活率:113.62%,119.38%,129.78%,169.93%;
100ng/LT+L-OHP(ug/ml):0.625,1.25,2.5,5
细胞存活率:144.98%,145.33%,158.70%,155.17%;
图4.D
ADM(ug/ml):0.00390625,0.015625,0.0625,0.25,1;
细胞存活率:95.22%,91.96%,87.19%,55.10%,39.92%;
100ng/LT+DM(ug/ml):0.00390625,0.015625,0.0625,0.25,1;
细胞存活率:193.94%,186.10%,171.62%,68.05%,43.69%;
图4.E
Epi-ADM(ug/ml):0.0032,0.016,0.08,0.4,2;
细胞存活率:87.88%,86.68%,73.79%,73.21%,71.15%;
100ng/LT+Epi-ADM(ug/ml):0.0032,0.016,0.08,0.4,2;
细胞存活率:89.59%,79.64%,77.97%,75.52%,75.30%;
图4.F
5-FU(ug/ml):0.00390625,0.015625,0.0625,0.25,1;
细胞存活率:62.41%,69.78%,90.32%,98.82%,87.23%;
100ng/LT+5-FU(ug/ml):0.00390625,0.015625,0.0625,0.25,1;
细胞存活率:146.08%,144.77%,131.53%,128.77%,119.55%;
图4.G
MMC(ug/ml):0.0001,0.001,0.01,0.1;
细胞存活率:77.50%,76.87%,79.51%,88.98%;
100ng/LT+MMC(ug/ml):0.0001,0.001,0.01,0.1;
细胞存活率:87.96%,82.41%,79.94%,80.22%;
图4.H
CTX(ug/ml):62.5,125,250,500,1000;
细胞存活率:90.22%,70.81%,66.64%,65.50%,37.23%;
100ng/LT+CTX(ug/ml):62.5,125,250,500,1000;
细胞存活率:195.38%,173.46%,151.25%,104.55%,51.71%;
图4.I
VCR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:91.39%,92.29%,96.42%,99.35;
100ng/LT+VCR(ug/ml):0.0001,0.001,0.01,0.1
细胞存活率:80.31%,79.80%,77.75%,74.99%;
图4.J
VNR(ug/ml):0.008,0.04,0.2,1,5;
细胞存活率:76.09%,74.49%,72.38%,69.15%,67.55%;
100ng/LT+VNR(ug/ml):0.008,0.04,0.2,1,5;
细胞存活率:85.62%,84.32%,82.45%,78.59%,77.41%;
具体实施方式
如本文所用,术语“淋巴毒素”、“LT”、“LTα”、“TNFβ”可互换使用,意指淋巴毒素LTα,包括来源于人、鼠、猪、马或牛的淋巴毒素。较佳地,是人淋巴毒素。此外,淋巴毒素可以是具有天然野生型序列的LT,也可以是具有突变序列(相对野生型序列而言)的衍生型或重组的LT。
本发明的LT突变体和药物组合物的给药方式没有特别限制,可以通过口服、局部、非肠道给药,例如肌肉、静脉、或皮下注射,或吸入喷雾等方式给药。优选方式是静脉注射给药。
当本发明中的LT突变体以片剂或胶囊形式口服时,剂量对于平均体重60-70公斤的成人而言在约1ug到1000ug范围内,或以注射剂方式非肠道给药,剂量约为1ug到500ug,可以每天一次或分几次给药。药物组合物的单元剂量通常包括范围为1ug-500ug的活性成分,典型地是1ug、5ug、10ug、25ug、50ug、100ug、200ug、300ug、400ug、500ug。
用本发明组合物治疗具体病症时所用的治疗活性成分的数量和给药方案,取决于多种因素,包括体重、年龄、性别、必然的医学症状、疾病轻重、给药途径及频率。这可以由医务人员确定。
本发明中采用的细胞株,包括:BGC-823(胃腺癌)、NCI-H157(非小细胞肺腺癌)、SW480(结肠癌)、SK-BR-3(转移性乳腺腺癌)、A375(黑色素瘤)、Hep2(喉癌)、HeLa(宫颈癌)7种上皮来源的肿瘤细胞,Raji(非霍奇金淋巴瘤)、Ramos(非霍奇金淋巴瘤)2种骨髓来源的肿瘤细胞购于中国科学院细胞库。
本发明中采用的化疗药物,包括:卡铂(CBDCA)、顺铂(CDDP)、奥沙利铂(L-OHP)、阿霉素(ADM)、5-氟尿嘧啶(5-FU)、长春新碱(VCR)、丝裂霉素(MMC)、环磷酰胺(CTX)、长春瑞滨(VNR)购于Sigma公司,表阿霉素(epi-ADM)购于Calbiochem公司。细胞培养基RPMI-1640培养基为Invitrogen公司产品,其他试剂为国产分析纯试剂。
本发明采用的重组人淋巴毒素为LT28-171,是野生型淋巴毒素氨基末端截去27个氨基酸的产物,其置备方法参见的中国专利CN00111884.6记载的方法制备。
制备的淋巴毒素可用水、生理盐水、细胞培养液等溶解和稀释,这可以由实验人员确定。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件,例如Sambrook等人,分子克隆:实验室手册(New York:Cold Spring HarborLaboratory Press,1989)中所述的条件,或按照制造厂商所建议的条件。
通用方法
BGC-823(胃腺癌)、NCI-H157(非小细胞肺腺癌)、SW480(结肠癌)、SK-BR-3(转移性乳腺腺癌)、A375(黑色素瘤)、Hep2(喉癌)、HeLa(宫颈癌)7种上皮来源的肿瘤细胞,Raji(非霍奇金淋巴瘤)、Ramos(非霍奇金淋巴瘤)2种骨髓来源的肿瘤细胞,分别以1.0×104细胞/孔接种96孔板,用RPMI-1640培养基,在37℃、5%CO2培养24h后加入药物。
药物处理实验分为以下4组:
(a)化疗药物组:卡铂(CBDCA)、顺铂(CDDP)、奥沙利铂(L-OHP)、阿霉素(ADM)、表阿霉素(epi-ADM)、5-氟尿嘧啶(5-FU)、丝裂霉素(MMC)、环磷酰胺(CTX)、长春新碱(VCR)、长春瑞滨(VNR)共10种化疗药物,各自稀释成系列浓度,根据每种药物的特性和所施加的细胞系的特点,通过预试验确定加药浓度,具体见实施例;
(b)淋巴毒素组:单加100ng/ml的淋巴毒素;
(c)淋巴毒素+化疗药物组:100ng/ml的LT与化疗药物按(a)项确定的浓度联合加药;
(d)空白对照组:加等量培养液。
继续培养48h后用MTS染色法检测细胞存活情况。获得数据进行统计学处理,协同作用、叠加作用确定按Basic toxicology(2nd Ed.1991,69-70)公开的以下公式计算:
Definitions of drug combination effects
synergistic | SF(a+b)<(SFa)(SFb) |
additivesubadditiveantagonistic | SF(a+b)=(SFa)(SFb)SF(a+b)>(SFa)(SFb)<SFb,when SFa>SFbSF(a+b)>(SFa)(SFb) |
SF:surviving fraction;a,b:drugs;(a+b):drugs incombination
Synergistic意为协同,additive意为叠加,subadditive意为亚叠加,antagonistic意为拮抗。
第一部分:rhLT对上皮来源的肿瘤的化疗增敏作用
实施例1.rhLT对BGC-823(胃癌)细胞的化疗增敏作用
实验结果见表1。卡铂(CBDCA)、顺铂(CDDP)、奥沙利铂(L-OHP)、阿霉素(ADM)在3个剂量组都呈现协同作用;5-FU在高剂量组、中间剂量组呈现协同作用;丝裂霉素(MMC)仅在高剂量组呈现协同作用;其他药物组为叠加或亚叠加作用。
表1 rhLT对BGC-823(胃癌)细胞的化疗增敏作用
BGC-823(%) | 1ug/mlCDDP | 0.5ug/mlCDDP | 0.25ug/mlCDDP | 50ug/mlCBDCA | 25ug/mlCBDCA | 12.5ug/mlCBDCA |
Drug(SFa) | 58.9±0.8 | 81.3±1.6 | 89.6±0.2 | 25.9±0.6 | 65.4±1.9 | 84.1±0.8 |
0.1ug/mlLT(SFb) | 95.6±1.7 | 95.6±1.7 | 95.6±1.7 | 91.4±7.9 | 91.4±7.9 | 91.4±7.9 |
Drug+LT(SFa+b) | 20.0±0.8 | 50.8±0.8 | 70.4±0.5 | 15.2±0.2 | 48.5±8.7 | 60.6±1.0 |
(SFa)(SFb) | 56.2±0.3 | 77.7±0.2 | 85.6±1.7 | 23.7±2.6 | 59.7±3.4 | 76.9±7.4 |
Combinedeffect | synergistic | synergistic | synergistic | synergistic | synergistic | synergistic |
p | 1.9E-07 | 6.1E-07 | 1.2E-04 | 4.5E-03 | 5.4E-03 | 2.7E-03 |
BGC-823(%) | 5ug/ml L-OHP | 2.5ug/mlL-OHP | 1.25ug/mlL-OHP | 10ng/mlVCR | 1ng/mlVCR | 0.1ng/mlVCR |
Drug(SFa) | 27.8±0.2 | 46.2±0.1 | 52.0±0.7 | 20.3±1.0 | 80.6±1.4 | 98.0±2.0 |
0.1ug/mlLT(SFb) | 94.7±3.3 | 94.7±3.3 | 94.7±3.3 | 86.5±3.0 | 86.5±3.0 | 86.5±3.0 |
Drug+LT(SFa+b) | 18.0±2.7 | 37.0±0.3 | 46.4±0.5 | 13.0±2.7 | 66.1±2.1 | 90.7±9.9 |
(SFa)(SFb) | 26.3±1.1 | 43.7±1.4 | 49.3±2.4 | 17.6±1.4 | 69.7±3.6 | 84.8±3.8 |
Combinedeffect | synergistic | synergistic | additive | additive | additive | additive |
p | 7.9E-03 | 1.3E-03 | 0.102 | 0.060 | 0.201 | 0.390 |
BGC-823(%) | 10ng/mlVNR | 1ng/mlVNR | 0.1ng/mlVNR | 1ug/mlADM | 0.5ug/mlADM | 0.25ug/mlADM |
Drug(SFa) | 43.5±3.5 | 88.4±1.3 | 93.8±7.4 | 4.1±0.2 | 24.1±5.4 | 94.6±0.4 |
0.1ug/mlLT(SFb) | 86.5±3.0 | 86.5±3.0 | 86.5±3.0 | 93.5±1.3 | 93.5±1.3 | 93.5±1.3 |
Drug+LT(SFa+b) | 35.7±1.1 | 86.2±2.1 | 89.9±4.6 | 3.7±0.5 | 7.3±0.4 | 84.9±0.3 |
(SFa)(SFb) | 37.5±1.7 | 76.4±3.2 | 81.0±3.7 | 3.8±0.2 | 22.6±5.4 | 88.5±0.9 |
Combinedeffect | additive | subadditive | additive | additive | synegiistic | synergistic |
p | 0.189 | 1.2E-02 | 0.060 | 0.293 | 7.9E-03 | 2.3E-03 |
BGC-823(%) | 80ng/mlepi-ADM | 16ng/mlepi-ADM | 3.2ng/mlepi-ADM | 50ug/ml 5-FU | 25ug/ml 5-FU | 12.5ug/ml5-FU |
Drug(SFa) | 60.7±0.4 | 72.2±6.8 | 91.3±5.7 | 87.9±0.3 | 93.5±0.9 | 94.2±1.3 |
0.1ug/mlLT(SFb) | 89.5±6.5 | 89.5±6.5 | 89.5±6.5 | 88.4±6.2 | 88.4±6.2 | 88.4±6.2 |
Drug+LT(SFa+b) | 50.0±0.6 | 68.4±8.2 | 87.1±2.4 | 48.6±0.3 | 68.1±3.4 | 79.7±1.6 |
(SFa)(SFb) | 54.3±2.6 | 64.8±6.1 | 81.9±6.2 | 77.8±5.2 | 82.6±5.0 | 83.8±7.0 |
Combinedeffect | synergistic | additive | additive | synergistic | synergistic | additive |
p | 4.8E-02 | 0.458 | 0.228 | 6.1E-04 | 1.4E-02 | 0.427 |
BGC-823(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 20ug/mlMMC | 5ug/mlMMC | 1.25ug/mlMMC |
Drug(SFa) | 49.0±1.3 | 68.3±0.7 | 72.3±0.8 | 29.9±1.5 | 62.8±4.0 | 79.7±6.3 |
0.1ug/mlLT(SFb) | 94.9±2.4 | 94.9±2.4 | 94.9±2.4 | 94.6±2.0 | 94.6±2.0 | 94.6±2.0 |
Drug+LT(SFa+b) | 46.7±0.4 | 65.6±0.4 | 68.4±2.9 | 21.6±4.0 | 58.7±2.9 | 75.4±3.5 |
(SFa)(SFb) | 46.5±1.1 | 64.8±1.4 | 68.6±1.4 | 28.3±2.0 | 59.4±2.6 | 75.3±4.4 |
Combinedeffect | additive | additive | additive | synergistic | additive | additive |
p | 0.843 | 0.414 | 0.903 | 0.059 | 0.776 | 0.974 |
实施例2.rhLT对NCI-H157(非小细胞肺腺癌)细胞的化疗增敏作用
实验结果见图1及表2。卡铂(CBDCA)、顺铂(CDDP)、奥沙利铂(L-OHP)在3个剂量组都呈现协同作用;阿霉素(ADM)在高剂量组、中间剂量组呈现协同作用;其他药物组为叠加或亚叠加作用。
表2、rhLT对NCI-H157(非小细胞肺腺癌)细胞的化疗增敏作用
NCI-H157(%) | 2.5ug/mlCDDP | 1.25ug/mlCDDP | 0.625ug/mlCDDP | 50ug/mlCBDCA | 25ug/mlCBDCA | 12.5ug/mlCBDCA |
Drug(SFa) | 45.6±0.3 | 71.0±0.7 | 87.9±0.6 | 59.0±1.0 | 79.1±0.4 | 86.2±0.2 |
0.1ug/mlLT(SFb) | 94.4±2.2 | 94.4±2.2 | 94.4±2.2 | 88.4±0.5 | 88.4±0.5 | 88.4±0.5 |
Drug+LT(SFa+b) | 9.8±0.3 | 40.4±1.1 | 63.2±0.7 | 50.2±0.2 | 67.5±0.5 | 69.0±0.2 |
(SFa)(SFb) | 43.1±1.3 | 67.1±2.3 | 83.0±1.4 | 52.1±0.2 | 69.9±0.8 | 76.2±0.7 |
Combinedeffect | synergistic | synergistic | synergistic | synergistic | synergistic | synergistic |
p | 1.9E-06 | 5.4E-05 | 2.6E-05 | 5.0E-02 | 1.0E-02 | 5.0E-05 |
NCI-H157(%) | 5ug/ml L-OHP | 2.5ug/mlL-OHP | 1.25ug/mlL-OHP | 62.5ng/mlVCR | 15.6ng/mlVCR | 3.9ng/mlVCR |
Drug(SFa) | 55.4±0.1 | 64.7±1.2 | 78.1±1.0 | 22.4±3.4 | 35.3±5.9 | 81.3±4.8 |
0.1ug/mlLT(SFb) | 90.0±0.1 | 90.0±0.1 | 90.0±0.1 | 88.5±7.5 | 88.5±7.5 | 88.5±7.5 |
Drug+LT(SFa+b) | 45.2±0.2 | 50.7±0.8 | 64.1±0.7 | 13.1±1.1 | 27.1±4.9 | 77.8±7.0 |
(SFa)(SFb) | 49.8±0.1 | 58.2±1.0 | 70.3±1.0 | 20.1±4.7 | 31.0±2.5 | 72.2±10.3 |
Combinedeffect | synergistic | synergistic | synergistic | additive | additive | additive |
p | 5.0E-06 | 5.2E-04 | 7.3E-04 | 0.065 | 0.289 | 0.477 |
NCI-H157(%) | 100ng/mlVNR | 10ng/mlVNR | 1ng/mlVNR | 0.75ug/mlADM | 0.19ug/mlADM | 0.05ug/mlADM |
Drug(SFa) | 23.4±4.1 | 80.3±6.8 | 97.7±3.4 | 15.4±0.5 | 48.6±0.7 | 75.9±0.5 |
0.1ug/mlLT(SFb) | 88.3±5.4 | 88.3±5.4 | 88.3±5.4 | 89.4±5.5 | 89.4±5.5 | 89.4±5.5 |
Drug+LT(SFa+b) | 12.6±1.7 | 52.5±5.6 | 91.4±1.4 | 12.2±1.4 | 39.7±0.1 | 60.9±0.2 |
(SFa)(SFb) | 20.8±4.9 | 71.0±4.4 | 86.2±4.3 | 13.8±1.3 | 43.5±3.3 | 67.8±3.9 |
Combinedeffect | additive | additive | additive | additive | additive | synergistic |
p | 5.1E-02 | 0.052 | 0.116 | 0.204 | 0.113 | 3.5E-02 |
NCI-H157(%) | 80ng/mlepi-ADM | 16ng/mlepi-ADM | 3.2ng/mlepi-ADM | 1ug/ml 5-FU | 0.25ug/ml5-FU | 0.625ug/ml5-FU |
Drug(SFa) | 68.3±1.5 | 81.7±3.7 | 94.2±2.1 | 42.2±2.5 | 60.6±0.5 | 66.8±2.4 |
0.1ug/mlLT(SFb) | 88.0±4.6 | 88.0±4.6 | 88.0±4.6 | 90.1±3.7 | 90.1±3.7 | 90.1±3.7 |
Drug+LT(SFa+b) | 54.7±2.1 | 70.0±5.5 | 90.3±5.3 | 30.8±5.0 | 51.61±2.0 | 61.2±0.8 |
(SFa)(SFb) | 60.0±1.9 | 72.0±7.0 | 82.8±2.5 | 38.4±1.9 | 54.6±2.7 | 60.1±1.3 |
Combinedeffect | synergistic | additive | additive | additive | additive | additive |
p | 3.0E-02 | 0.603 | 0.088 | 0.069 | 0.193 | 0.276 |
NCI-H157(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 5ug/mlMMC | 1.25ug/mlMMC | 0.31ug/mlMMC |
Drug(SFa) | 49.1±0.8 | 65.5±4.5 | 69.4±6.3 | 34.1±2.7 | 55.9±2.3 | 73.1±1.3 |
0.1ug/ml | 91.3±3.6 | 91.3±3.6 | 91.3±3.6 | 89.7±3.1 | 89.7±3.1 | 89.7±3.1 |
LT(SFb) | ||||||
Drug+LT(SFa+b) | 43.7±1.1 | 52.7±4.2 | 56.8±3.0 | 28.9±5.7 | 51.5±6.1 | 66.2±6.5 |
(SFa)(SFb) | 44.9±2.5 | 59.7±1.8 | 63.2±3.3 | 30.5±1.4 | 50.2±3.7 | 65.6±6.1 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.490 | 0.056 | 6.8E-02 | 0.662 | 0.763 | 0.871 |
实施例3.rhLT对SW480(结肠癌)细胞的化疗增敏作用
实验结果见表3。卡铂(CBDCA)、顺铂(CDDP)在3个剂量组都呈现协同作用;奥沙利铂(L-OHP)高剂量组、中间剂量组呈现协同作用;阿霉素(ADM)在高剂量组、低剂量组呈现协同作用;其他药物组为叠加作用。
表3、rhLT对SW480(结肠癌)细胞的化疗增敏作用
SW480(%) | 2.5ug/mlCDDP | 1.25ug/mlCDDP | 0.625ug/mlCDDP | 50ug/mlCBDCA | 25ug/mlCBDCA | 12.5ug/mlCBDCA |
Drug(SFa) | 46.1±1.2 | 59.7±1.6 | 79.3±5.7 | 32.6±0.3 | 60.41±0.3 | 79.9±1.3 |
0.1ug/mlLT(SFb) | 87.1±4.2 | 87.1±4.2 | 87.1±4.2 | 83.9±1.5 | 83.9±1.5 | 83.9±1.5 |
Drug+LT(SFa+b) | 17.3±1.5 | 34.5±2.3 | 58.5±1.9 | 17.5±0.4 | 33.0±1.0 | 55.1±2.5 |
(SFa)(SFb) | 40.15±0.9 | 51.9±1.2 | 68.9±1.6 | 27.4±0.7 | 50.7±1.1 | 67.0±0.1 |
Combinedeffect | synergistic | synergistic | synergistic | synergistic | synergistic | synergistic |
p | 2.5E-04 | 2.8E-04 | 1.9E-03 | 4.4E-05 | 5.0E-05 | 3.7E-03 |
SW480(%) | 3.5ug/mlL-OHP | 1.75ug/mlL-OHP | 0.88ug/mlL-OHP | 100ng/mlVCR | 25ng/mlVCR | 6.25ng/mlVCR |
Drug(SFa) | 45.2±1.0 | 54.6±2.7 | 61.2±7.8 | 44.4±2.8 | 55.6±3.7 | 58.4±3.0 |
0.1ug/mlLT(SFb) | 93.0±1.6 | 93.0±1.6 | 93.0±1.6 | 89.5±2.6 | 89.5±2.6 | 89.5±2.6 |
Drug+LT(SFa+b) | 37.2±0.1 | 42.6±3.3 | 49.7±1.6 | 40.4±2.5 | 52.9±1.9 | 55.8±1.5 |
(SFa)(SFb) | 42.1±1.6 | 50.8±3.3 | 57.0±8.2 | 37.9±2.6 | 49.7±2.1 | 52.3±4.0 |
Combinedeffect | synergistic | synergistic | additive | additive | additive | additive |
p | 6.2E-03 | 3.9E-02 | 0.206 | 0.743 | 0.119 | 0.227 |
SW480(%) | 100ng/mlVNR | 10ng/mlVNR | 1ng/mlVNR | 1ug/mlADM | 0.5ug/mlADM | 0.25ug/mlADM |
Drug(SFa) | 41.1±4.9 | 87.0±2.1 | 93.5±4.4 | 18.9±1.1 | 39.7±0.6 | 54.0±6.1 |
0.1ug/mlLT(SFb) | 88.1±4.0 | 88.1±4.0 | 88.1±4.0 | 92.1±2.1 | 92.1±2.1 | 92.1±2.1 |
Drug+LT(SFa+b) | 27.4±4.1 | 79.6±1.8 | 89.1±1.4 | 16.3±0.6 | 29.6±3.4 | 53.5±3.2 |
(SFa)(SFb) | 36.3±6.0 | 76.6±2.5 | 82.4±6.3 | 17.4±1.4 | 36.6±1.4 | 49.9±6.7 |
Combinedeffect | additive | additive | additive | additive | synergistic | additive |
p | 0.098 | 0.173 | 0.148 | 0.300 | 2.9E-02 | 0.447 |
SW480(%) | 80ng/mlepi-ADM | 16ng/mlepi-ADM | 3.2ng/mlepi-ADM | 25ug/ml 5-FU | 12.5ug/ml5-FU | 6.25ug/ml5-FU |
Drug(SFa) | 33.7±5.0 | 66.1±1.3 | 88.0±5.9 | 43.7±4.9 | 49.4±0.1 | 56.4±3.5 |
0.1ug/mlLT(SFb) | 86.4±1.9 | 86.4±1.9 | 86.4±1.9 | 93.5±1.6 | 90.1±3.7 | 90.1±3.7 |
Drug+LT(SFa+b) | 14.1±0.8 | 58.8±2.9 | 78.8±6.1 | 34.4±1.6 | 42.5±2.2 | 51.4±1.0 |
(SFa)(SFb) | 29.1±5.0 | 57.1±0.1 | 76.0±3.5 | 40.8±3.9 | 46.2±0.9 | 52.7±2.3 |
Combinedeffect | synergistic | additive | additive | additive | additive | additive |
p | 6.7E-03 | 0.364 | 0.531 | 0.057 | 0.058 | 0.446 |
SW480(%) | 1000ug/mlCTX | 500ug/mlCTX | 250ug/mlCTX | 2.5ug/mlMMC | 0.625ug/mlMMC | 0.16ug/mlMMC |
Drug(SFa) | 47.3±3.5 | 80.2±2.9 | 89.2±3.3 | 50.5±7.2 | 79.9±3.9 | 88.9±1.3 |
0.1ug/mlLT(SFb) | 89.1±3.0 | 89.1±3.0 | 89.1±3.0 | 90.1±2.0 | 90.1±2.0 | 89.7±3.1 |
Drug+LT(SFa+b) | 41.5±2.8 | 70.8±0.4 | 79.7±1.9 | 47.1±9.3 | 76.8±5.1 | 83.0±2.6 |
(SFa)(SFb) | 42.5±4.3 | 71.5±4.7 | 79.5±2.1 | 45.5±6.6 | 72.0±3.1 | 80.1±2.9 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.646 | 0.804 | 0.903 | 0.822 | 0.241 | 0.283 |
实施例4.rhLT对SK-BR-3(转移性乳腺腺癌)细胞的化疗增敏作用
实验结果见图2及表4。卡铂(CBDCA)、顺铂(CDDP)、奥沙利铂(L-OHP)、表阿霉素(epi-ADM)在3个剂量组都呈现协同作用;阿霉素(ADM)仅在在高剂量组呈现协同作用;丝裂霉素(MMC)在高剂量组、低剂量组呈现协同作用;其他药物组为叠加或亚叠加作用。
表4、rhLT对SK-BR-3(转移性乳腺腺癌)细胞的化疗增敏作用
SK-BR-3(%) | 2ug/mlCDDP | 1ug/mlCDDP | 0.5ug/mlCDDP | 20ug/mlCBDCA | 10ug/mlCBDCA | 5ug/mlCBDCA |
Drug(SFa) | 61.5±3.1 | 79.3±0.4 | 88.3±0.7 | 60.1±2.1 | 72.3±2.7 | 96.5±3.7 |
0.1ug/mlLT(SFb) | 75.7±0.4 | 75.7±0.4 | 75.7±0.4 | 74.5±0.9 | 74.5±0.9 | 74.5±0.9 |
Drug+LT(SFa+b) | 34.2±1.6 | 46.3±3.3 | 59.8±1.7 | 21.9±2.6 | 34.3±3.3 | 48.9±2.5 |
(SFa)(SFb) | 46.6±2.1 | 60.1±0.1 | 66.9±0.9 | 44.8±2.1 | 53.9±1.4 | 71.9±1.9 |
Combinedeffect | synergistic | synergistic | synergistic | synergistic | synergistic | synergistic |
p | 1.2E-03 | 2.0E-03 | 2.7E-03 | 2.9E-04 | 7.2E-04 | 2.2E-04 |
SK-BR-3(%) | 5ug/ml L-OHP | 2.5ug/mlL-OHP | 1.25ug/mlL-OHP | 100ng/mlVCR | 10ng/mlVCR | 1ng/mlVCR |
Drug(SFa) | 48.4±0.4 | 52.5±1.7 | 61.8±2.1 | 24.6±1.4 | 29.7±2.1 | 98.9±4.4 |
0.1ug/mlLT(SFb) | 77.5±1.7 | 77.5±1.7 | 77.5±1.7 | 85.7±3.3 | 85.7±3.3 | 85.7±3.3 |
Drug+LT(SFa+b) | 29.0±2.2 | 34.4±2.6 | 35.6±1.2 | 21.3±1.8 | 27.0±2.5 | 71.8±4.1 |
(SFa)(SFb) | 37.5±1.1 | 40.7±0.4 | 47.9±0.6 | 21.2±2.0 | 25.5±1.8 | 84.9±7.0 |
Combinedeffect | synergistic | synergistic | synergistic | additive | additive | additive |
p | 3.9E-03 | 1.5E-02 | 8.6E-05 | 0.950 | 0.448 | 0.226 |
SK-BR-3(%) | 100ng/mlVNR | 10ng/mlVNR | 1ng/mlVNR | 1ug/mlADM | 0.5ug/mlADM | 0.25ug/mlADM |
Drug(SFa) | 26.5±2.6 | 32.9±4.3 | 97.0±2.3 | 20.8±0.7 | 23.6±0.9 | 36.1±3.2 |
0.1ug/ml | 85.7±3.3 | 85.7±3.3 | 85.7±3.3 | 80.3±5.6 | 80.3±5.6 | 80.3±5.6 |
LT(SFb) | ||||||
Drug+LT(SFa+b) | 24.3±2.8 | 28.7±1.8 | 87.2±2.5 | 13.7±0.7 | 22.3±1.2 | 31.2±0.9 |
(SFa)(SFb) | 22.7±1.8 | 28.3±4.6 | 83.2±2.7 | 16.7±1.7 | 19.0±2.1 | 29.1±4.6 |
Combinedeffect | additive | additive | additive | synergistic | additive | additive |
p | 0.450 | 0.902 | 0.127 | 4.6E-02 | 0.075 | 0.481 |
SK-BR-3(%) | 250ng/mlepi-ADM | 62.5ng/mlepi-ADM | 15.6ng/mlepi-ADM | 50ug/ml 5-FU | 25ug/ml 5-FU | 12.5ug/ml5-FU |
Drug(SFa) | 44.4±1.3 | 58.6±2.3 | 95.0±2.2 | 44.3±6.3 | 49.3±1.3 | 51.1±1.3 |
0.1ug/mlLT(SFb) | 89.0±2.1 | 89.0±2.1 | 89.0±2.1 | 90.6±0.3 | 90.6±0.3 | 90.6±0.3 |
Drug+LT(SFa+b) | 31.5±1.9 | 36.1±2.3 | 69.4±4.6 | 31.9±1.0 | 40.6±2.8 | 45.3±0.7 |
(SFa)(SFb) | 39.6±2.0 | 52.1±2.7 | 84.6±1.0 | 40.1±5.6 | 44.7±1.4 | 46.3±1.1 |
Combinedeffect | synergistic | synergistic | synergistic | additive | additive | additive |
p | 7.5E-03 | 1.4E-03 | 4.9E-03 | 0.067 | 0.089 | 0.249 |
SK-BR-3(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 2ug/mlMMC | 0.5ug/mlMMC | 0.125ug/mlMMC |
Drug(SFa) | 49.3±0.1 | 75.2±1.7 | 83.0±4.5 | 20.1±2.3 | 43.1±2.7 | 81.8±1.1 |
0.1ug/mlLT(SFb) | 88.6±3.8 | 88.6±3.8 | 88.6±3.8 | 88.7±8.4 | 88.7±8.4 | 88.7±8.4 |
Drug+LT(SFa+b) | 45.2±0.3 | 63.6±0.7 | 75.4±0.1 | 10.3±0.5 | 31.6±2.2 | 53.8±7.5 |
(SFa)(SFb) | 43.7±1.9 | 66.7±3.8 | 73.6±6.1 | 17.7±0.4 | 38.3±6.0 | 72.5±5.9 |
Combinedeffect | additive | additive | additive | synergistic | additive | synergistic |
p | 0.251 | 0.245 | 0.626 | 3.7E-05 | 0.144 | 2.8E-02 |
实施例5.rhLT对A375(黑色素瘤)细胞的化疗增敏作用
实验结果见表5。L-OHP3个剂量组、CDDP中间剂量组和低剂量组、CBDCA高剂量组呈现协同作用;MMC中间剂量组和低剂量组呈现协同作用;其他药物组为叠加或亚叠加作用。
表5、rhLT对A375(黑色素瘤)细胞的化疗增敏作用
A375(%) | 0.5ug/mlCDDP | 0.25ug/mlCDDP | 0.125ug/mlCDDP | 10ug/mlCBDCA | 5ug/mlCBDCA | 2.5ug/mlCBDCA |
Drug(SFa) | 62.6±0.6 | 77.6±1.3 | 88.3±1.6 | 68.8±2.0 | 72.5±3.4 | 78.4±3.9 |
0.1ug/mlLT(SFb) | 75.9±0.6 | 75.9±0.6 | 75.9±0.6 | 79.2±1.3 | 79.2±1.3 | 79.2±1.3 |
Drug+LT(SFa+b) | 47.1±1.7 | 53.3±0.6 | 56.8±1.2 | 52.1±0.4 | 59.9±4.4 | 66.2±2.8 |
(SFa)(SFb) | 47.5±0.1 | 58.8±0.6 | 67.0±0.7 | 54.5±0.6 | 57.4±1.7 | 62.1±4.2 |
Combinedeffect | additive | synergistic | synergistic | synergistic | additive | additive |
p | 0.745 | 2.8E-04 | 1.9E-04 | 6.2E-03 | 0.416 | 0.234 |
A375(%) | 0.5ug/mlL-OHP | 0.13ug/mlL-OHP | 0.03ug/mlL-OHP | 62.5ng/mlVCR | 15.6ng/mlVCR | 3.9ng/mlVCR |
Drug(SFa) | 43.7±1.5 | 87.6±4.0 | 98.1±3.2 | 41.9±8.2 | 46.7±6.6 | 75.2±2.2 |
0.1ug/mlLT(SFb) | 71.0±3.6 | 71.0±3.6 | 71.0±3.6 | 92.1±5.8 | 92.1±5.8 | 92.1±5.8 |
Drug+LT(SFa+b) | 25.9±1.3 | 37.4±1.1 | 38.7±2.0 | 38.0±3.1 | 40.2±5.0 | 57.3±7.5 |
(SFa)(SFb) | 31.1±2.6 | 62.1±0.3 | 69.6±1.2 | 38.9±10.0 | 42.7±3.4 | 69.0±0.5 |
Combinedeffect | synergistic | synergistic | synergistic | additive | additive | additive |
p | 3.8E-02 | 2.8E-06 | 2.2E-05 | 0.888 | 0.514 | 0.055 |
A375(%) | 100ng/mlVNR | 10ng/mlVNR | 1ng/mlVNR | 1ug/mlADM | 0.5ug/mlADM | 0.25ug/mlADM |
Drug(SFa) | 30.5±3.1 | 60.3±4.7 | 98.4±4.0 | 12.5±0.9 | 39.1±0.5 | 50.7±2.0 |
0.1ug/mlLT(SFb) | 42.4±0.4 | 42.4±0.4 | 42.4±0.4 | 86.8±6.3 | 86.8±6.3 | 86.8±6.3 |
Drug+LT(SFa+b) | 28.3±0.5 | 33.8±4.7 | 44.9±2.1 | 11.8±0.9 | 32.6±2.2 | 48.9±4.7 |
(SFa)(SFb) | 12.9±1.4 | 25.1±1.1 | 41.7±1.6 | 10.9±1.5 | 33.9±2.0 | 44.0±1.5 |
Combinedeffect | subadditive | subadditive | additive | additive | additive | additive |
p | 5.2E-05 | 4.8E-02 | 0.100 | 0.448 | 0.511 | 0.160 |
A375(%) | 80ng/mlepi-ADM | 16ng/mlepi-ADM | 3.2ng/mlepi-ADM | 25ug/ml 5-FU | 12.5ug/ml5-FU | 6.25ug/ml5-FU |
Drug(SFa) | 21.3±3.1 | 47.1±1.3 | 76.7±3.7 | 14.0±1.4 | 20.1±0.8 | 30.9±0.7 |
0.1ug/mlLT(SFb) | 88.7±1.7 | 88.7±1.7 | 88.7±1.7 | 83.7±5.2 | 83.7±5.2 | 83.7±5.2 |
Drug+LT(SFa+b) | 18.7±3.0 | 39.1±1.8 | 61.0±1.5 | 10.9±1.3 | 18.0±1.0 | 24.1±0.9 |
(SFa)(SFb) | 18.9±3.1 | 41.8±2.0 | 68.1±4.6 | 11.8±1.9 | 16.9±1.8 | 25.9±1.0 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.950 | 0.156 | 0.065 | 0.561 | 0.403 | 0.086 |
A375(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 1.25ug/mlMMC | 0.31ug/mlMMC | 0.08ug/mlMMC |
Drug(SFa) | 74.3±0.4 | 93.4±1.8 | 97.2±2.5 | 29.0±0.7 | 75.7±1.0 | 94.3±1.6 |
0.1ug/mlLT(SFb) | 42.4±0.4 | 42.4±0.4 | 42.4±0.4 | 82.0±1.7 | 82.0±1.7 | 82.0±1.7 |
Drug+LT(SFa+b) | 33.4±1.5 | 42.2±1.4 | 43.5±1.8 | 25.3±0.9 | 45.0±1.4 | 54.4±3.0 |
(SFa)(SFb) | 31.5±0.4 | 39.6±1.1 | 41.2±0.9 | 23.8±1.0 | 62.1±0.5 | 77.3±0.3 |
Combinedeffect | additive | additive | additive | additive | synergistic | synergistic |
p | 0.100 | 0.061 | 0.103 | 0.133 | 3.7E-05 | 2.0E-04 |
实施例6.rhLT对Hep2(喉癌)细胞的化疗增敏作用
实验结果见表5。ADM、5-FU3个剂量组呈现协同作用;CBDCA、L-OHP的高剂量组和中间剂量组以及CDDP、epi-ADM的高剂量组呈现协同作用。其他药物组为叠加作用。
表6、rhLT对Hep2(喉癌)细胞的化疗增敏作用
Hep2(%) | 2.5ug/mlCDDP | 1.25ug/mlCDDP | 0.625ug/mlCDDP | 100ug/mlCBDCA | 50ug/mlCBDCA | 25ug/mlCBDCA |
Drug(SFa) | 37.9±2.3 | 60.5±1.0 | 82.0±1.6 | 41.8±0.5 | 68.6±0.7 | 78.4±0.7 |
0.1ug/mlLT(SFb) | 89.7±3.3 | 89.7±3.3 | 89.7±3.3 | 87.7±0.8 | 87.7±0.8 | 87.7±0.8 |
Drug+LT(SFa+b) | 28.4±0.4 | 53.8±2.2 | 70.4±1.7 | 26.6±2.2 | 57.4±1.5 | 71.3±1.9 |
(SFa)(SFb) | 33.9±0.8 | 54.3±2.9 | 73.5±1.3 | 36.7±0.1 | 60.1±0.1 | 68.8±1.3 |
Combinedeffect | synergistic | additive | additive | synergistic | synergistic | additive |
p | 4.5E-04 | 0.829 | 0.072 | 1.3E-03 | 3.3E-02 | 0.124 |
Hep2(%) | 5ug/ml L-OHP | 2.5ug/mlL-OHP | 1.25ug/mlL-OHP | 10ng/mlVCR | 0.63ng/mlVCR | 0.04ng/mlVCR |
Drug(SFa) | 37.8±0.1 | 42.8±1.0 | 46.4±0.9 | 71.9±6.3 | 81.2±6.3 | 90.5±4.7 |
0.1ug/mlLT(SFb) | 92.0±8.3 | 92.0±8.3 | 92.0±8.3 | 88.5±3.6 | 88.5±3.6 | 88.5±3.6 |
Drug+LT(SFa+b) | 28.0±0.3 | 30.8±2.8 | 38.1±4.0 | 49.2±5.4 | 56.89±7.0 | 66.7±5.7 |
(SFa)(SFb) | 34.8±3.2 | 39.4±4.4 | 42.7±4.6 | 69.3±12.4 | 72.0±8.5 | 80.2±7.4 |
Combinedeffect | synergistic | synergistic | additive | additive | additive | additive |
p | 2.3E-02 | 4.6E-02 | 0.262 | 0.062 | 0.074 | 0.065 |
Hep2(%) | 100ng/mlVNR | 10ng/mlVNR | 1ng/mlVNR | 1ug/mlADM | 0.5ug/mlADM | 0.25ug/mlADM |
Drug(SFa) | 13.4±1.5 | 80.4±1.9 | 93.9±1.7 | 7.3±0.5 | 28.4±2.5 | 60.2±1.1 |
0.1ug/mlLT(SFb) | 94.8±4.2 | 94.8±4.2 | 94.8±4.2 | 91.3±4.2 | 91.3±4.2 | 91.3±4.2 |
Drug+LT(SFa+b) | 10.8±1.2 | 74.2±3.9 | 92.3±1.3 | 3.1±0.3 | 13.0±0.6 | 38.1±0.4 |
(SFa)(SFb) | 12.6±1.0 | 76.3±4.8 | 88.9±2.7 | 6.7±0.8 | 25.9±1.1 | 55.0±3.5 |
Combinedeffect | additive | additive | additive | synergistic | synergistic | synergistic |
p | 0.099 | 0.582 | 0.120 | 1.9E-03 | 5.5E-05 | 1.2E-03 |
Hep2(%) | 250ng/mlepi-ADM | 62.5ng/mlepi-ADM | 15.6ng/mlepi-ADM | 25ug/ml 5-FU | 12.5ug/ml5-FU | 6.25ug/ml5-FU |
Drug(SFa) | 45.8±1.0 | 59.8±2.3 | 81.8±1.5 | 28.7±0.2 | 33.2±1.0 | 37.2±0.9 |
0.1ug/mlLT(SFb) | 94.8±4.2 | 94.8±4.2 | 94.8±4.2 | 92.2±1.9 | 92.2±1.9 | 92.2±1.9 |
Drug+LT(SFa+b) | 25.6±2.5 | 58.9±3.4 | 72.9±2.6 | 13.2±0.4 | 16.2±0.6 | 21.2±0.3 |
(SFa)(SFb) | 43.1±1.2 | 56.8±4.6 | 77.5±4.8 | 26.4±0.3 | 30.6±1.6 | 34.3±1.5 |
Combinedeffect | synergistic | additive | additive | synergistic | synergistic | synergistic |
p | 3.5E-04 | 0.561 | 0.216 | 1.4E-06 | 1.2E-04 | 1.2E-04 |
Hep2(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 12.5ug/mlMMC | 6.25ug/mlMMC | 3.13ug/mlMMC |
Drug(SFa) | 78.9±2.1 | 87.6±5.6 | 94.9±2.2 | 9.9±0.7 | 57.3±2.9 | 69.6±5.6 |
0.1ug/mlLT(SFb) | 92.6±1.6 | 92.6±1.6 | 92.6±1.6 | 93.8±6.1 | 93.8±6.1 | 93.8±6.1 |
Drug+LT(SFa+b) | 76.6±2.8 | 85.4±1.8 | 91.7±3.8 | 7.8±1.1 | 42.0±5.5 | 66.2±1.9 |
(SFa)(SFb) | 73.1±0.7 | 81.3±3.8 | 87.8±0.5 | 9.3±0.1 | 53.9±6.2 | 65.1±1.1 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.103 | 0.156 | 0.156 | 0.087 | 0.067 | 0.403 |
实施例7.rhLT对HeLa(宫颈癌)细胞的化疗增敏作用
CDDP高剂量组、CBDCA 3个剂量组、L-OHP高剂量组和中间剂量组呈现协同作用;5-FU 3个剂量组呈现协同作用,其他药物组为叠加作用。
表7、rhLT对HeLa(宫颈癌)细胞的化疗增敏作用
HeLa(%) | 5ug/mlCDDP | 2.5ug/mlCDDP | 1.25ug/mlCDDP | 10ug/mlCBDCA | 5ug/mlCBDCA | 2.5ug/mlCBDCA |
Drug(SFa) | 63.0±1.0 | 72.9±1.0 | 75.4±0.5 | 75.9±2.2 | 83.9±2.5 | 89.1±2.1 |
0.1ug/mlLT(SFb) | 94.5±0.5 | 94.5±0.5 | 94.5±0.5 | 89.7±1.6 | 89.7±1.6 | 89.7±1.6 |
Drug+LT(SFa+b) | 58.2±0.3 | 69.7±0.6 | 72.8±4.7 | 62.4±2.7 | 64.0±1.2 | 70.9±0.5 |
(SFa)(SFb) | 59.5±0.6 | 68.8±0.5 | 71.3±0.1 | 68.0±0.8 | 75.2±0.9 | 79.9±3.3 |
Combinedeffect | synergistic | additive | additive | synergistic | synergistic | synergistic |
p | 2.8E-02 | 0.123 | 0.597 | 1.4E-02 | 4.7E-02 | 2.9E-02 |
HeLa(%) | 1ug/ml L-OHP | 0.5ug/mlL-OHP | 0.25ug/mlL-OHP | 100ng/mlVCR | 10ng/mlVCR | 1ng/mlVCR |
Drug(SFa) | 65.2±0.6 | 71.8±0.5 | 81.9±1.4 | 27.9±1.0 | 82.6±0.8 | 94.2±1.1 |
0.1ug/ml | 92.1±9.4 | 92.1±9.4 | 92.1±9.4 | 93.7±3.0 | 93.7±3.0 | 93.7±3.0 |
LT(SFb) | ||||||
Drug+LT(SFa+b) | 44.9±5.6 | 54.3±2.8 | 65.82±3.8 | 26.5±0.6 | 74.3±2.5 | 93.2±2.9 |
(SFa)(SFb) | 60.1±6.6 | 66.1±6.3 | 75.3±6.4 | 26.1±0.5 | 77.4±3.1 | 88.2±1.8 |
Combinedeffect | synergistic | synergistic | additive | additive | additive | additive |
p | 3.9E-02 | 4.1E-02 | 0.092 | 0.498 | 0.250 | 0.067 |
HeLa(%) | 100ng/mlVNR | 10ng/mlVNR | 1ng/mlVNR | 1.25ug/mlADM | 0.63ug/mlADM | 0.31ug/mlADM |
Drug(SFa) | 28.4±3.7 | 86.2±3.4 | 94.0±2.4 | 6.1±0.5 | 35.9±1.2 | 40.6±0.3 |
0.1ug/mlLT(SFb) | 93.7±3.0 | 93.7±3.0 | 93.7±3.0 | 91.8±6.2 | 91.8±6.2 | 91.8±6.2 |
Drug+LT(SFa+b) | 27.9±3.5 | 82.5±3.7 | 92.2±3.2 | 4.1±1.1 | 31.2±2.3 | 35.8±1.0 |
(SFa)(SFb) | 26.6±3.0 | 80.8±5.7 | 88.0±4.0 | 5.6±0.1 | 33.0±3.3 | 37.3±2.8 |
Combinedeffect | additive | additive | additive | additive | additive | ad ditive |
p | 0.645 | 0.697 | 0.233 | 0.074 | 0.478 | 0.451 |
HeLa(%) | 250ng/mlepi-ADM | 62.5ng/mlepi-ADM | 15.6ng/mlepi-ADM | 25ug/ml 5-FU | 12.5ug/ml5-FU | 6.25ug/ml5-FU |
Drug(SFa) | 52.6±1.0 | 69.5±1.0 | 82.5±4.1 | 48.7±4.5 | 54.4±2.6 | 65.9±2.1 |
0.1ug/mlLT(SFb) | 94.7±3.2 | 94.7±3.2 | 94.7±3.2 | 91.5±4.8 | 91.5±4.8 | 91.5±4.8 |
Drug+LT(SFa+b) | 46.3±1.3 | 67.3±1.3 | 73.1±1.0 | 36.4±4.8 | 41.5±2.7 | 44.7±4.8 |
(SFa)(SFb) | 49.8±2.6 | 65.8±2.4 | 78.2±6.1 | 44.4±1.8 | 49.7±0.2 | 60.2±1.2 |
Combinedeffect | additive | additive | additive | synergistic | synergistic | synergistic |
p | 0.106 | 0.385 | 0.231 | 2.7E-03 | 6.8E-03 | 3.6E-05 |
HeLa(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 20ug/mlMMC | 1.25ug/mlMMC | 0.08ug/mlMMC |
Drug(SFa) | 81.3±4.1 | 84.2±4.7 | 86.1±4.4 | 37.8±1.8 | 74.1±1.3 | 90.3±1.6 |
0.1ug/ml000 LT(SFb) | 92.9±4.3 | 92.9±4.3 | 92.9±4.3 | 91.3±3.5 | 91.3±3.5 | 91.3±3.5 |
Drug+LT(SFa+b) | 78.7±3.8 | 82.1±3.6 | 83.1±3.9 | 29.6±1.8 | 65.6±1.8 | 85.2±5.7 |
(SFa)(SFb) | 75.7±3.7 | 78.1±0.8 | 79.0±0.4 | 34.5±3.0 | 67.7±3.8 | 82.4±4.6 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.563 | 0.132 | 0.242 | 0.073 | 0.441 | 0.548 |
第二部分rhLT对骨髓来源肿瘤细胞的化疗增敏作用
实施例8.rhLT对Raji(非霍奇金淋巴瘤)细胞的化疗增敏作用
实验结果见图3及表8。所用药物均未表现协同作用。CBDCA和5-FU的高剂量组、ADM的3个剂量组呈现拮抗作用,其他药物组为叠加作用。
表8、rhLT对Raji(非霍奇金淋巴瘤)细胞的化疗增敏作用
Raji(%) | 5ug/mlCDDP | 0.31ug/mlCDDP | 0.02ug/mlCDDP | 50ug/mlCBDCA | 25ug/mlCBDCA | 12.5ug/mlCBDCA |
Drug(SFa) | 42.3±6.5 | 85.5±6.7 | 94.4±3.1 | 37.9±1.3 | 66.2±8.5 | 89.1±1.5 |
0.1ug/mlLT(SFb) | 102.3±2.7 | 102.3±2.7 | 102.3±2.7 | 103.0±8.1 | 103.0±8.1 | 103.0±8.1 |
Drug+LT(SFa+b) | 43.6±5.9 | 86.3±1.4 | 95.7±2.4 | 43.1±1.4 | 70.6±9.0 | 97.2±4.2 |
(SFa)(SFb) | 43.4±8.2 | 87.3±3.7 | 96.5±0.3 | 38.9±1.7 | 68.7±14.1 | 91.8±5.7 |
Combinedeffect | additive | additive | additive | antagonistic | additive | additive |
p | 0.982 | 0.682 | 0.616 | 3.2E-02 | 0.851 | 2.5E-01 |
Raji(%) | 2ug/mlL-OHP | 0.5ug/mlL-OHP | 0.125ug/mlL-OHP | 100ng/mlVCR | 10ng/mlVCR | 1ng/mlVCR |
Drug(SFa) | 51.1±3.1 | 91.3±1.6 | 96.5±6.0 | 84.2±5.9 | 88.8±1.5 | 90.8±3.6 |
0.1ug/mlLT(SFb) | 104.0±10.9 | 104.0±10.9 | 104.0±10.9 | 104.6±3.7 | 104.6±3.7 | 104.6±3.7 |
Drug+LT(SFa+b) | 59.8±2.4 | 106.7±2.7 | 108.7±9.6 | 87.4±6.6 | 90.9±2.9 | 94.3±3.6 |
(SFa)(SFb) | 53.3±8.8 | 94.8±8.3 | 100.8±16.8 | 87.9±5.0 | 92.9±2.9 | 95.0±7.0 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.285 | 0.077 | 0.520 | 0.915 | 0.450 | 0.891 |
Raji(%) | 5ug/mlVNR | 0.2ug/mlVNR | 0.01ug/mlVNR | 0.63ug/mlADM | 0.31ug/mlADM | 0.16ug/mlADM |
Drug(SFa) | 32.6±0.6 | 25.7±1.1 | 30.6±2.5 | 37.2±3.2 | 49.2±2.3 | 92.4±4.8 |
0.1ug/mlLT(SFb) | 105.2±4.2 | 105.2±4.2 | 105.2±4.2 | 104.0±2.9 | 104.0±2.9 | 104.0±2.9 |
Druf+LT(SFa+b) | 38.3±2.1 | 29.5±7.1 | 32.0±1.0 | 47.3±3.7 | 68.1±7.8 | 102.0±2.6 |
(SFa)(SFb) | 34.3±4.8 | 27.0±0.1 | 32.3±4.8 | 38.3±2.2 | 51.0±3.8 | 95.2±2.3 |
Combinedeffect | additive | additive | additive | antagonistic | antagonistic | antagonistic |
p | 0.276 | 0.637 | 0.923 | 2.3E-02 | 2.7E-02 | 2.8E-02 |
Raji(%) | 2000ng/mlepi-ADM | 80ng/mlepi-ADM | 3.2ug/mlepi-ADM | 188ug/ml5-FU | 47ug/ml 5-FU | 12ug/ml 5-FU |
Drug(SFa) | 54.0±4.1 | 11.2±2.8 | 22.3±1.5 | 50.6±5.2 | 71.1±6.8 | 82.2±2.4 |
0.1ug/mlLT(SFb) | 101.7±6.1 | 101.7±6.1 | 101.7±6.1 | 103.9±6.6 | 103.9±6.6 | 103.9±6.6 |
Drug+LT(SFa+b) | 62.8±5.3 | 18.1±3.3 | 22.0±5.1 | 62.0±4.7 | 74.6±5.7 | 85.6±5.1 |
(SFa)(SFb) | 54.7±0.9 | 11.5±3.5 | 22.7±2.9 | 52.3±2.1 | 73.5±2.4 | 85.5±7.9 |
Combinedeffect | additive | additive | additive | antagonistic | additive | additive |
p | 0.060 | 0.078 | 0.838 | 3.1E-02 | 0.787 | 0.987 |
Raji(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 6.25ug/mlMMC | 1.56ug/mlMMC | 0.39ug/mlMMC |
Drug(SFa) | 63.3±5.6 | 86.0±3.5 | 92.1±2.8 | 33.4±2.8 | 53.1±9.6 | 74.7±4.9 |
0.1ug/mlLT(SFb) | 104.1±7.4 | 104.1±7.4 | 104.1±7.4 | 103.2±8.6 | 103.2±8.6 | 103.2±8.6 |
Drug+LT(SFa+b) | 70.1±4.1 | 88.0±2.3 | 98.4±5.6 | 37.7±4.0 | 62.1±7.1 | 81.2±3.0 |
(SFa)(SFb) | 65.6±1.2 | 89.7±10.1 | 95.7±3.9 | 34.3±0.1 | 54.2±5.4 | 77.4±11.4 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.142 | 0.790 | 0.532 | 0.225 | 0.202 | 0.601 |
实施例9.rhLT对Romos(非霍奇金淋巴瘤)细胞的化疗增敏作用
实验结果见图4及表9。所用药物均未表现协同作用。CDDP低剂量组、VNR高剂量组、ADM高剂量组和低剂量组以及CTX、MMC的高剂量组和中间剂量组,以及5-FU的3个剂量组呈现拮抗作用,其他药物组为叠加作用。
表9、rhLT对Romos(非霍奇金淋巴瘤)细胞的化疗增敏作用
Ramos(%) | 3ug/mlCDDP | 1.5ug/mlCDDP | 0.75ug/mlCDDP | 50ug/mlCBDCA | 25ug/mlCBDCA | 12.5ug/mlCBDCA |
Drug(SFa) | 142.6±8.9 | 108.4±11.4 | 89.5±5.5 | 112.3±8.9 | 100.2±5.3 | 93.3±5.8 |
0.1ug/mlLT(SFb) | 147.1±9.7 | 147.1±9.7 | 147.1±9.7 | 136.9±8.1 | 136.9±8.1 | 136.9±8.1 |
Drug+LT(SFa+b) | 195.2±8.7 | 162.9±2.7 | 150.2±4.0 | 141.7±9.0 | 129.9±8.2 | 133.0±5.0 |
(SFa)(SFb) | 210.2±20.9 | 158.7±6.3 | 131.0±0.6 | 153.2.±3.1 | 136.8±0.9 | 128.0±15.5 |
Combinedeffect | additive | additive | antagonistic | additive | additive | additive |
p | 0.409 | 0.355 | 1.3E-03 | 0.103 | 0.223 | 0.029 |
Ramos(%) | 2.5ug/mlL-OHP | 1.25ug/mlL-OHP | 0.63ug/mlL-OHP | 10ng/mlVCR | 1ng/mlVCR | 0.1ng/mlVCR |
Drug(SFa) | 129.8±6.4 | 119.,4±8.3 | 113.6±8.4 | 96.4±2.3 | 92.3±1.4 | 91.4±1.7 |
0.1ug/mlLT(SFb) | 133.8±5.2 | 133.8±5.2 | 133.8±5.2 | 84.5±2.8 | 84.5±2.8 | 84.5±2.8 |
Drug+LT(SFa+b) | 158.7±4.9 | 145.3±13.1 | 145.0±13.4 | 79.8±0.8 | 79.8±2.3 | 80.3±1.7 |
(SFa)(SFb) | 173.9±15.3 | 160.1±17.3 | 152.4±17.2 | 81.4±2.1 | 78.0±3.4 | 77.2±3.8 |
Combinedeffect | additive | additive | additive | additive | additive | additive |
p | 0.177 | 0.304 | 0.589 | 0.095 | 0.487 | 0.268 |
Ramos(%) | 5ug/mlVNR | 0.2ug/mlVNR | 0.01ug/mlVNR | 0.25ug/mlADM | 0.63ug/mlADM | 0.16ug/mlADM |
Drug(SFa) | 67.6±0.75.1 | 72.1±1.3 | 76.1±6.2 | 55.1±2.2 | 87.2±9.2 | 92.0±5.6 |
0.1ug/mlLT(SFb) | 106.0±8.9 | 106.0±8.9 | 106.0±8.9 | 132.5±6.4 | 132.5±6.4 | 132.5±6.4 |
Drug+LT(SFa+b) | 77.4±2.9 | 82.1±1.1 | 85.6±1.8 | 68.0±7.2 | 171.6±6.7 | 186.1±14.0 |
(SFa)(SFb) | 71.3±0.7 | 76.7±5.0 | 81.0±13.4 | 72.9±0.7 | 116.0±17.9 | 122.1±13.4 |
Combinedeffect | antagonistic | additive | additive | additive | antagonistic | antagonistic |
p | 2.5E-02 | 0.139 | 0.589 | 0.308 | 7.3E-03 | 4.7E-03 |
Ramos(%) | 2000ng/mlepi-ADM | 80ng/mlepi-ADM | 3.2ug/mlepi-ADM | 62.5ng/ml5-FU | 15.6ng/ml5-FU | 3.9ng/ml 5-FU |
Drug(SFa) | 71.2±6.3 | 73.8±2.7 | 87.9±1.6 | 90.3±4.6 | 69.8±3.9 | 62.4±2.6 |
0.1ug/mlLT(SFb) | 111.0±6.0 | 111.0±6.0 | 111.0±6.0 | 128.3±6.6 | 128.3±6.6 | 128.3±6.6 |
Drug+LT(SFa+b) | 75.3±1.4 | 78.0±2.6 | 89.6±1.3 | 131.5±4.3 | 144.8±14.4 | 146.1±5.9 |
(SFa)(SFb) | 78.7±2.8 | 82.0±7.4 | 97.6±7.0 | 115.7±0.2 | 89.4±0.5 | 80.2±7.5 |
Combinedeffect | additive | additive | additive | antagonistic | antagonistic | antagonistic |
p | 0.128 | 0.424 | 0.123 | 3.2E-03 | 2.7E-03 | 2.8E-04 |
Ramos(%) | 1000ug/mlCTX | 250ug/mlCTX | 62.5ug/mlCTX | 100ug/mlMMC | 25ug/mlMMC | 6.25ug/mlMMC |
Drug(SFa) | 37.2±5.5 | 66.6±9.5 | 90.2±7.4 | 89.0±3.7 | 79.5±3.8 | 76.9±3.7 |
0.1ug/mlLT(SFb) | 134.9±9.8 | 134.9±9.8 | 134.9±9.8 | 84.5±2.8 | 84.5±2.8 | 84.5±2.8 |
Drug+LT(SFa+b) | 51.7±4.1 | 151.3±7.8 | 195.4±5.4 | 80.2±3.0 | 79.9±3.6 | 82.4±4.3 |
(SFa)(SFb) | 49.8±3.8 | 90.5±19.3 | 121.2±1.3 | 75.2±5.6 | 67.2±5.2 | 65.0±5.3 |
Combinedeffect | additive | antagonistic | antagonistic | additive | antagonistic | antagonistic |
p | 0.597 | 7.2E-03 | 2.0E-05 | 0.244 | 2.6E-02 | 1.2E-02 |
Claims (9)
1.淋巴毒素在制备增加上皮来源的肿瘤对化疗药物敏感性的药物中的应用。
2.如权利要求1所述的应用,其特征在于,其中所说的淋巴毒素包括来源于人、鼠、猪、马或牛的淋巴毒素。
3.如权利要求2所述的应用,其特征在于,其中所说的淋巴毒素为来源于人的淋巴毒素及其衍生物。
4.如权利要求3所述的应用,其特征在于,其中所说的淋巴毒素包括LT1-171、LT24-171、LT28-171。
5.如权利要求1所述的应用,其特征在于,其中所说的上皮来源的肿瘤包括非小细胞肺癌、乳腺癌、喉癌、结直肠癌、子宫颈癌、黑色素瘤或胃癌。
6.如权利要求1所述的应用,其特征在于,其中所说的化疗药物包括铂类药物、蒽环类药物、5-FU或丝裂霉素。
7.如权利要求3所述的应用,其特征在于,其中所说的化疗药物为铂类抗肿瘤药物。
8.如权利要求4所述的应用,其特征在于,其中所说的化疗药物为卡铂、顺铂或奥沙利铂。
9.如权利要求1所述的应用,其特征在于,其中所说的增加上皮来源的肿瘤对化疗药物敏感性的药物指在对患有上皮来源肿瘤患者在化疗前、同时或化疗后给与,以提高患者对化疗药物耐受性或增加化疗药物疗效的药物。
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WO2009062344A1 (fr) * | 2007-11-16 | 2009-05-22 | Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. | Utilisation de lymphotoxine pour sensibiliser des cellules tumorales à des médicaments chimiothérapeutiques |
CN107213456A (zh) * | 2017-05-25 | 2017-09-29 | 苏州华测生物技术有限公司 | 淋巴毒素衍生物的新用途 |
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TR200002203T2 (tr) * | 1998-01-30 | 2000-12-21 | Biogen, Inc | Lemfotoksin (LT) sentezlenme yolunun inhibitörleri kullanılarak foliküler lemfomaların tedavisi. |
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CN107213456A (zh) * | 2017-05-25 | 2017-09-29 | 苏州华测生物技术有限公司 | 淋巴毒素衍生物的新用途 |
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