WO2016062266A1 - 氨氯地平在制备抑制癌症的医药组合物中的用途 - Google Patents

氨氯地平在制备抑制癌症的医药组合物中的用途 Download PDF

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WO2016062266A1
WO2016062266A1 PCT/CN2015/092632 CN2015092632W WO2016062266A1 WO 2016062266 A1 WO2016062266 A1 WO 2016062266A1 CN 2015092632 W CN2015092632 W CN 2015092632W WO 2016062266 A1 WO2016062266 A1 WO 2016062266A1
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cancer
amlodipine
10min
use according
cells
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French (fr)
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陈丘泓
庄秀美
魏宗德
萧乃文
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朗齐生物医学股份有限公司
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Definitions

  • the present invention relates to the use of new indications for amlodipine drugs, in particular the use of amlodipine drugs for inhibiting a variety of cancers.
  • Amlodipine (Amlodipine or Amlodipine besylate, pulsed ingot (Norvasc, Pfizer brand name) and other generic drugs, can be with besylate, mesylate or maleic acid, etc. It is a "long-acting calcium channel blocker (CCB)" as an antihypertensive drug and a dihydropyridine (DHP) class for the treatment of angina pectoris.
  • Amlodipine is a "dihydropyridine calcium antagonist” (calcium antagonist, or slow channel blocker) whose mechanism is to inhibit the movement of "calcium ions" into vascular smooth muscle cells and cardiac muscle cells. .
  • amlodipine belongs to a kind of "peripheral arterial vasodilator" which acts directly on vascular smooth muscle, which reduces peripheral vascular resistance and lowers blood pressure.
  • Amlodipine is used to treat high blood pressure and coronary heart disease.
  • Amlodipine is a drug that has long been approved by the FDA and has a large number of drug transfer and human research results.
  • amlodipine has the potential to inhibit cancer cells.
  • cancer has long been the leading cause of death worldwide, and the number of cancer patients has increased year by year. Therefore, treating cancer has become an important issue.
  • cancer drug treatment whether it is chemotherapy or target treatment, is intended to prevent cancer cells from replicating and dividing to block the spread and spread of tumors. According to statistics, only about five per million new drugs can enter the first Phase clinical trials. Further, many cancer cells successively develop drug resistance, which greatly reduces the effectiveness of drug use, and ultimately leads to failure of cancer treatment. This shows that drug development has a certain degree of difficulty.
  • the present invention aims at the development of new indications for amlodipine drugs, and achieves the goal of new use of old drugs.
  • amlodipine drugs have no or only minimal toxicity to normal cells, but amlodipine has a selective effect between tumor cells.
  • the present invention provides a use of the amlodipine drug for the preparation of a pharmaceutical composition for inhibiting cancer, wherein the pharmaceutical composition comprises amlodipine besylate and a pharmaceutically acceptable salt.
  • the cancer is selected from one or more of a chest-related cancer, an abdominal cavity-related cancer, an endocrine-related cancer, and a digestive tract-related cancer.
  • the cancer is selected from the group consisting of an osteosarcoma-related cancer and a skin cancer-related cancer.
  • chest cavity related cancer refers to lung cancer
  • the abdominal cavity-related cancer is selected from the group consisting of bladder cancer or/and kidney cancer or/and cervical cancer.
  • the endocrine-related cancer is selected from one or more of prostate cancer, breast cancer, and ovarian cancer.
  • the digestive tract-related cancer is selected from one or more of the group consisting of gastric cancer, liver cancer, colon cancer, pancreatic cancer, and tongue cancer.
  • the effective concentration of the amlodipine drug is from 20 mg/kg to 500 mg/kg per day.
  • Figure 1 shows the use of the amlodipine of the present invention for inhibiting cancer cell analysis results
  • FIG. 1 shows the effect of amlodipine on tumor volume
  • Figure 3 shows the inhibitory effect of high-dose and low-dose amlodipine tumor growth
  • Subculture of cell lines of different cancer types including cancerous lung cancer, gastric cancer, liver cancer, rectal cancer, skin cancer, cervical cancer, prostate cancer, bladder cancer, breast cancer, blood cancer, pancreatic cancer, ovarian cancer, tongue cancer Osteosarcoma, kidney cancer, and the control group also used normal cells of the kidney (HEK293 (Kidney)), fibroblast HFW (fibroblast), and lung epithelial cell BEAS-2B (Lung Epithelial) for testing.
  • HEK293 Kidney
  • fibroblast HFW fibroblast
  • BEAS-2B Long Epithelial
  • the cells corresponding to different species should be counted with the corresponding culture solution (Table 1), and the number of cells should be counted, and 2 ⁇ 10 6 cells should be returned. Then, the culture medium in which the cell strain was cultured was added to a volume of 10 ml, and the culture was continued for 2-3 days. The cells were then counted and dispensed into 96-well plates where the number of cells per well was fixed at 3000 and the volume was 100 ul.
  • IC50 is the semi-inhibitory concentration (or semi-inhibition rate). It is a very important data in the indirect competition ELISA standard curve, and the standard curve is an S-shaped curve.
  • the OD value of the control group without drug addition was B0
  • the OD value of the experimental group to which the drug was added was B
  • B/B0% was called the binding rate
  • the concentration of the drug at the binding rate was 50%. It is called IC50.
  • the smaller the value of IC50 the stronger the inhibitory effect of the drug.
  • the original culture solution in the 96-well plate was aspirated, and a commercially available drug having a concentration of 10 ⁇ m and a volume of 100 ul was added to each well. After 72 hours, 100 ul of diluted WST-1 reagent was added to each well, and the dilution ratio was the culture solution and The volume ratio of the WST-1 stock solution was 9:1, and finally the total volume of each well plate was 200 ul. Then the 96-well plate was placed at 37 ° C for 30-90 minutes, using an elisa reader (ELISA) on the OD450. The absorbance values were detected and the survival rate of each cancer cell line was calculated.
  • ELISA elisa reader
  • the analysis of the inhibitory effect of amlodipine on pleural cavity-related cancer cells was mainly tested on two kinds of lung cancer cells.
  • the cancer cell lines were A549 and H1650, respectively, and the results of cancer cell inhibition experiments were performed 4 times each, and the calculation was performed.
  • the average value is shown in Table 2.
  • the analysis of the inhibitory effect of amlodipine on peritoneal cancer-related cancer cells was mainly tested on two kinds of cells related to abdominal cancer-related cancer cells.
  • the bladder cancer cell lines were TSGH and T24, respectively (Table 3), cervical cancer cell lines. They were HeLa cell line and C-33A cell line (Table 4), and the kidney cancer cell line was 786-O (Table 5).
  • the results of cancer cell inhibition experiments were performed 4 times each, and the average value was calculated. The results are shown in Table 3. -5 is shown.
  • prostate cancer cell lines were PC-3 and LNCap, respectively (Table 6), breast cancer cell lines.
  • MCF7 and MDA-MB-231 were tested for cancer cell inhibition four times each, and the average value was calculated. The results are shown in Table 6-8.
  • the gastric cancer cell lines were AGS and MKN-45, respectively (Table 9), liver cancer cell lines. They were HepG2 and Hep3B, respectively (Table 10), the colorectal cancer cell lines were HCT116-wt and LoVo cell lines (Table 11), and the pancreatic cancer cell lines were AsPC and BxPC cell lines, respectively (Table 12).
  • the tongue cancer cell line was a SAS cell strain (Table 13), and the results of the cancer cell inhibition experiments were performed four times each, and the average value was calculated. The results are shown in Table 9-13.
  • the osteosarctic cancer cell line is U2OS cell line (Table 14)
  • the skin cancer cell lines are A375 and BCC cell lines (Table 15), each of which is done 4 times.
  • the cancer cells inhibited the experimental results and the average values were calculated. The results are shown in Tables 14-15.
  • the normal kidney cell line was HEK293 cell line (Table 16)
  • the normal fibroblast cell line was HFW cell line (Table 17)
  • the normal lung epithelial cell line was The BEAS-2B cell line (Table 18) was subjected to four times of cancer cell inhibition test results, and the average value was calculated. The results are shown in Table 16-18.
  • mice Female BALB/cAnN.Cg-Foxn1nu/CrlNarl mice were used as samples (purchased from National Laboratory Animal Center), weighing 21 ⁇ 1g, subcutaneously injected into gastric cancer cells (AGS) and randomly divided into cages.
  • the test drugs were divided into three groups: Normal control group, low dose (100 mg/kg/day), high dose (200 mg/kg/day).
  • the tumor formed more than 100 mm3, the drug was administered by intraperitoneal injection every day; the tumor size was measured twice a week, and the tumor volume measurement formula was as follows: (L ⁇ W2); L represents the longest diameter of the tumor; W represents the shortest diameter of the tumor.
  • the low dose and the high dose of ammonia chloride have a good inhibitory effect on the tumor, and the weight of the mice in each group did not decrease significantly during the experiment, thus indicating amlodipine regardless of Both high and low doses can make the tested mice have good health without death during the treatment.
  • high and low doses of amlodipine can effectively reduce tumor volume growth and simultaneously reduce tumor volume, wherein high dose of amlodipine has a better effect.

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Abstract

本发明提供了氨氯地平在制备治疗癌症的医药组合物中的用途，所述癌症包括肺癌、膀胱癌、肾脏癌、子宫颈癌、前列腺癌、乳癌、卵巢癌、胃癌、肝癌、大肠癌、胰脏癌、舌癌等。

Description

氨氯地平药物在制备抑制癌症的医药组合物中的用途 技术领域
本发明涉及氨氯地平药物的新适应症的应用，尤其所述氨氯地平药物具有抑制多种癌症的用途。
背景技术
氨氯地平(Amlodipine或Amlodipine besylate、脉优锭(Norvasc、辉瑞公司商标名)及其它学名药、可与苯磺酸(besylate)、甲磺酸酯(mesylate)或马来酸(maleic acid)等制备成复方药)是一种作为抗高血压药和治疗心绞痛的二氢吡啶(DHP)类的"长效钙通道阻滞药(CCB)"。氨氯地平是一种"二氢吡啶类钙拮抗剂"(钙离子拮抗剂、或慢通道阻滞剂)，其机制为抑制"钙离子"移动到血管平滑肌细胞和心肌细胞(cardiac muscle cell)。因此，氨氯地平是属于一种"外周动脉血管扩张剂"(peripheral arterial vasodilator)会直接作用于血管平滑肌上，使外周血管阻力减少进而血压降低。氨氯地平是用来治疗高血压及冠状动脉性心脏病。氨氯地平是早已被FDA所认可的用药，具有大量药物机转及人体研究成果资料。
由于临床应用上的明显差异，因此从来没有人认为氨氯地平具有抑制癌症细胞的可能性。
癌症长期高居全球死因之首，且罹患癌症人数更是逐年攀升，因此治疗癌症俨然成为重要的课题。一般来说，癌症药物治疗无论是化学治疗或标靶治疗，目的多是让癌细胞无法复制、分裂，来阻断肿瘤的蔓延扩张。根据统计，平均每一万个新药约只有五个能够进入第一 期临床试验。进一步，许多癌细胞相继产生抗药性，使药物的使用成效大幅降低，最终导致癌症治疗失败。由此可见药物开发具有一定的困难程度。
因此，如何能让癌症药物的快速的可以被开发出来，并且尽可能的减少临床失败的机率，在癌症病学上是一个非常急迫又重要的课题。
发明内容
为解决上述的问题，本发明针对氨氯地平药物进行新适应症的研发，而达到老药新用的目标。
经过实验设计结果显示氨氯地平药物对正常细胞没有或仅有微小的毒性，但氨氯地平在肿瘤细胞之间具有选择性的影响。
本发明提供一种制备氨氯地平药物在制备抑制癌症的医药组合物中的用途，其中所述医药组合物包含氨氯地平药物(Amlodipine besylate)及药学上可接受的盐类所组成。
本发明一实施例中，其中所述癌症选自胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
本发明一实施例中，其中所述癌症选自骨肉瘤相关癌症、皮肤癌相关癌症。
本发明一实施例中，其中所述胸腔相关癌症指的是肺癌。
本发明一实施例中，其中所述腹腔相关癌症选自膀胱癌或/和肾脏癌或/和子宫颈癌。
本发明一实施例中，其中所述内分泌相关癌症选自前列腺癌、乳癌、卵巢癌中的一种或多种。
本发明一实施例中，其中所述消化道相关癌症选自胃癌、肝癌、大肠癌、胰脏癌及舌癌中的一种或多种。
本发明一实施例中，其中所述氨氯地平药物的有效剂量浓度为每日20mg/kg～500mg/kg。
附图说明
图1显示本发明氨氯地平用药应用于抑制癌细胞分析结果
图2显示氨氯地平用药可对肿瘤体积的效果
图3显示高剂量及低剂量氨氯地平肿瘤生长的抑制效果
具体实施方式
各种癌症细胞株建立
将不同癌症类型的细胞株进行继代培养，癌症细胞种类包含肺癌、胃癌、肝癌、直肠癌、皮肤癌、子宫颈癌、前列腺癌、膀胱癌、乳癌、血癌、胰腺癌、卵巢癌、舌癌、骨肉瘤、肾脏癌，并且对照组亦使用肾脏(HEK293(Kidney))、纤维母细胞HFW(fibroblast)、肺部上皮细胞BEAS-2B(Lung Epithelial)的正常细胞做测试。(表一)
先将各细胞于培养液培养后，由于各细胞的属性不同，因此针对不同种的细胞也要用相对应的培养液(表一)，计算细胞数目，回种2×106个细胞数，然后加入培养该细胞株的培养液补至体积为10ml，继续培养2-3天。之后将细胞计数，并分装至96孔盘，其中每孔的细胞数目固定为3000个，且体积为100ul。
IC50即半抑制浓度(或称半抑制率)。在间接竞争ELISA标准曲线中是一个非常重要的数据，标准曲线是一个S型曲线。ICELISA中，不添加药物的对照组的OD值定为B0，添加了药物的实验组的OD值为B，B/B0％就叫做结合率，在结合率为50％时所对应的药物的浓度就叫做IC50。一般IC50的数值越小表示药物的抑制效果越强。
表一、癌症测试细胞株及其培养所用的培养液
Figure PCTCN2015092632-appb-000001
细胞存活分析方法
将96孔盘中原有的培养液吸掉，每孔加入浓度10um、体积100ul的市售药物，放置72小时后，每孔再加入100ul已稀释的WST-1试剂，该稀释比例为培养液与WST-1原液的体积比为9∶1，最后每个孔盘的总体积为200ul，然后将96孔盘放置于37℃，30～90分钟，利用elisa reader(酶联免疫检测仪)于OD450侦测吸光值，并计算各癌症细胞株的存活率。
氨氯地平药对于各种癌细胞分析结果
氨氯地平对胸腔相关癌症细胞抑制效果的测试
本分析氨氯地平对胸腔相关癌症细胞抑制效果的测试，主要针对两种肺癌细胞进行测试，癌细胞株分别为A549和H1650两个细胞株，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果如表二所示。
表二、氨氯地平对肺癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
A549 103.63 138.67 107.04 91.91 110.31
  1-10min 2-20min 3-20min 4-20min 平均
H1650 103.6 97.5 116.6 123.2 110.2
氨氯地平对腹腔相关癌症细胞抑制效果的测试
本分析氨氯地平对腹腔相关癌症细胞抑制效果的测试，主要针对两种腹腔相关癌症种类细胞进行测试，膀胱癌细胞株分别为TSGH和T24两个细胞株(表三)，子宫颈癌细胞株分别为HeLa细胞株与C-33A细胞株(表四)，肾脏癌细胞株为786-O(表五)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果如表3-5所示。
表三、氨氯地平对膀胱癌相关癌症细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
TSGH 34.41 35.42 35.90 39.26 36.2
  1-30min 2-20min 3-20min 4-20min 平均
T24 108.0 82.3 92.2 89.9 93.1
表四、氨氯地平对子宫颈癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
HeLa 93.70 103.69 97.06 110.70 101.29
  1 2 3 4 平均
C-33A 32.7 33.1 32.7 36.4 33.7
表五、氨氯地平对肾脏癌相关癌症细胞抑制测试
  1 2 3 4 平均
786-O 70.9 94.0 47.7 80.1 73.2
氨氯地平对内分泌相关癌症细胞抑制效果的测试
本分析氨氯地平对腹腔相关癌症细胞抑制效果的测试，主要针对三种内分泌相关癌症种类细胞进行测试，前列腺癌细胞株分别为PC-3和LNCap两个细胞株(表六)，乳癌细胞株分别为MCF7和MDA-MB-231两个细胞株(表七)，卵巢癌细胞株分别为 NIH-OVCAR-3细胞株和TOV-21G(表八)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果如表6-8所示。
表六、氨氯地平对前列腺癌相关癌症细胞抑制测试
Figure PCTCN2015092632-appb-000002
表七、氨氯地平对乳癌相关癌症细胞抑制测试
  0612-10min 0614-10min 0616-10min 0619-10min 平均
MCF7 73.83 82.90 76.46 88.76 80.49
  0612-10min 0614-10min 0616-10min 0619-10min 平均
MDA-MB-231 92.35 84.94 60.81 92.75 82.71
表八、氨氯地平对卵巢癌相关癌症细胞抑制测试
  7-3-30min 7-4-30min 7-7-30min 7-4-30min 平均
NIH-OVCAR-3 85.5 86.5 85.0 109.3 91.6
  7-3-30min 7-4-30min 7-7-30min 7-4-30min 平均
TOV-21G 104.8 85.5 88.7 95.2 93.5
氨氯地平对消化道相关癌症细胞抑制效果的测试
分析氨氯地平对消化道相关癌症细胞抑制效果的测试，主要针对五种消化道相关癌症种类细胞进行测试，胃癌细胞株分别为AGS和MKN-45两个细胞株(表九)，肝癌细胞株分别为HepG2和Hep3B两个细胞株(表十)，大肠癌细胞株分别为HCT116-wt和LoVo细胞株(表十一)，胰脏癌细胞株分别为AsPC和BxPC细胞株(表十二)，舌癌细胞株为SAS细胞株(表十三)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果如表9-13所示。
表九、氨氯地平对胃癌相关癌症细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
AGS 11.50 11.42 12.94 12.88 12.2
  0510-10min 0512-10min 0515-10min 0517-10min 平均
MKN-45 76.45 100.48 86.70 82.11 86.4
表十、氨氯地平对肝癌相关癌症细胞抑制测试
  0524-20min 0526-20min 0529-20min 0531-20min 平均
HepG2 90.26 92.51 104.32 92.94 95.01
  0612-20min 0614-20min 0616-20min 0619-20min 平均
Hep3B 119.61 149.06 107.82 117.19 123.42
表十一、氨氯地平对大肠癌相关癌症细胞抑制测试
  0602-30min 0605-10min 0607-10min 0609-10min 平均
HCT116-wt 80.65 96.84 76.17 59.35 78.26
  0616-10min 0619-10min 0621-10min 0623-10min 平均
LoVo 84.12 76.35 100.28 81.51 85.56
表十二、氨氯地平对胰脏癌相关癌症细胞抑制测试
  1-7-3-30min 1-7-4-30min 1-7-7-30min 1-4-30min 平均
AsPC 82.0 93.9 97.0 78.3 87.8
  3-7-3-30min 3-7-4-30min 3-7-7-30min 3-4-30min 平均
BxPC 74.8 124.1 82.5 115.0 99.1
表十三、氨氯地平对舌癌相关癌症细胞抑制测试
  6-26-10min 6-28-10min 6-30-10min 7-3-10min 平均
SAS 87.95 67.29 109.10 114.86 94.80
氨氯地平对其他癌症细胞抑制效果的测试
分析氨氯地平对其他类型癌正进行测试，骨肉癌细胞株为U2OS细胞株(表十四)，皮肤癌细胞株分别为A375和BCC两个细胞株(表十五)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果如表14-15所示。
表十四、氨氯地平对骨肉瘤相关癌症细胞抑制测试
  6-26-10min 6-28-10min 6-30-10min 7-3-10min 平均
U2OS 61.80 65.44 67.75 89.25 71.06
表十五、氨氯地平对皮肤癌相关癌症细胞抑制测试
  0602-30min 0605-10min 0607-10min 0609-10min 平均
A375 96.57 138.30 143.16 168.64 136.67
  0602-30min 0605-10min 0607-10min 0609-10min 平均
BCC 59.60 111.99 89.23 151.09 102.98
对照组实验设计
氨氯地平对正常细胞抑制效果的测试
分析氨氯地平对多种正常细胞进行测试，正常肾脏细胞株为HEK293细胞株(表十六)，正常纤维母细胞细胞株为HFW细胞株(表十七)，正常肺部上皮细胞细胞株为BEAS-2B细胞株(表十八)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果如表16-18所示。
表十六、氨氯地平对正常肾脏细胞抑制测试
  0602-30min 0605-30min 0607-30min 0609-30min 平均
HEK293 87.83 106.24 96.85 96.93 96.96
表十七、氨氯地平对正常纤维母细胞抑制测试
  0612-10min 0614-10min 0616-10min 0619-10min 平均
HFW 88.57 85.34 105.67 78.27 89.46
表十八、氨氯地平对正常肺部上皮细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
BEAS-2B 80.87 87.51 88.48 59.33 79.05
针对氨氯地平对各种癌症细胞抑制效果汇整于表十九中，清楚看出氨氯地平对于多项癌症有明显的抑制效果。经过发明人实验结果，氨氯地平药物对于不同的癌症细胞有明显的抑制效果。(图一)
表十九、氨氯地平对各种癌症细胞抑制效果的汇整
癌症细胞 抑制效果
肺癌 110.28
膀胱癌 64.66
子宫颈癌 67.49
前列腺癌 73.20
乳癌 68.18
卵巢癌 81.60
胃癌 92.55
肝癌 49.31
大肠癌 109.21
胰脏癌 81.91
舌癌 93.47
骨肉癌 94.80
皮肤癌 71.06
正常细胞 抑制效果
肾脏 119.82
纤维母细胞 96.96
肺部上皮细胞 89.46
动物实验分析
本实验使用雌性BALB/cAnN.Cg-Foxn1nu/CrlNarl小鼠为样本(购自国家实验动物中心)，体重为21±1g，皮下注射胃癌细胞(AGS)后随机分笼，测试药物分成三组:正常对照组、低剂量(100mg/kg/day)、高剂量(200mg/kg/day)。肿瘤形成超过100mm3后，每天采取腹腔注射方式给予药物；每周测量肿瘤大小两次，肿瘤体积测量公式如下：(L×W2)；L代表肿瘤最长直径；W代表肿瘤最短直径。
表二十、氨氯地平于动物实验对癌症对癌症之抑制效果
Figure PCTCN2015092632-appb-000003
Figure PCTCN2015092632-appb-000004
依据第2图的结果，低剂量与高剂量的氨氯地平均对肿瘤具有良好的抑制效果，且于实验过程中各组小鼠的重量均未出现明显降低的现象，因此表示氨氯地平不论高低剂量在治疗过程均能使受测小鼠具有良好的健康状态而不死亡。
依据第3图的结果，高低剂量的氨氯地平可有效减缓肿瘤体积增长，并可同时减少肿瘤体积，其中以高剂量的氨氯地平具有较佳的效果。
上列详细说明是针对本发明之一可行实施例的具体说明，惟该实施例并非用以限制本发明的专利范围，凡未脱离本发明技艺精神所为的等效实施或变更，均应包含于本发明的专利范围中。

Claims (8)

  1. 一种氨氯地平药物在制备抑制癌症的医药组合物中的用途，其特征是，所述医药组合物包含氨氯地平药物及药学上可接受的盐类所组成。
  2. 如权利要求1所述的用途，其特征是，所述癌症是选自由胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
  3. 如权利要求1所述的用途，其特征是，所述癌症的选自由骨肉瘤相关癌症、皮肤癌相关癌症、血癌相关癌症中一种或多种。
  4. 如权利要求2所述的用途，其特征是，所述胸腔相关癌症为肺癌。
  5. 如权利要求2所述的用途，其特征是，所述腹腔相关癌症选自膀胱癌或/和子宫颈癌。
  6. 如权利要求2所述的用途，其特征是，所述内分泌相关癌症是选自由前列腺癌、乳癌、卵巢癌中的一种或多种。
  7. 如权利要求2所述的用途，其特征是，所述消化道相关癌症系选自由胃癌、肝癌、大肠癌、胰脏癌、舌癌中的一种或多种。
  8. 如权利要求1所述的用途，其特征是，所述有效剂量浓度为每日20mg/kg～500mg/kg。
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