CN113786397A - 一种莪术提取物在制备乳腺癌骨转移的药物中的应用 - Google Patents
一种莪术提取物在制备乳腺癌骨转移的药物中的应用 Download PDFInfo
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Abstract
本发明公开了一种莪术提取物在制备乳腺癌骨转移的药物中的应用。莪术提取物meso‑Hannokinol在制备治疗乳腺癌转移的药物中的应用，优选莪术提取物meso‑Hannokinol在制备治疗乳腺癌骨转移的药物中的应用。本申请通过实验验证莪术提取物meso‑Hannokinol能够降低乳腺癌细胞的迁移能力从而预防骨转移的发生；能够降低乳腺癌造成的骨溶解和骨破坏来减少乳腺癌骨转移造成的骨损伤；能够有效抑制了裸鼠体内乳腺癌细胞的骨转移，从而莪术提取物meso‑Hannokinol可用于开发抗乳腺癌骨转移的相关药物。
Description
技术领域
本发明涉及中医药技术，具体涉及一种莪术提取物在制备乳腺癌骨转移的药物中的应用。
背景技术
乳腺癌是目前世界上女性最常见的恶性肿瘤之一，大约有70％的患者在癌症晚期发生转移。乳腺癌转移具有器官选择性，骨组织是最容易发生转移的部位，其转移比例远超肝、肺、肾等器官，约70％的转移情况为骨转移，胸椎、腰椎、肋骨和髋关节等均是骨转移常见部位，一旦发生骨转移，患者5年生存率就只有20％-30％。乳腺癌骨转移常引起顽固性骨痛、高钙血症、病理性骨折、功能障碍的一系列骨相关疾病，严重影响生活质量，同时也可导致患者遭受贫血、骨折、截瘫、高血钙、疼痛和恶病质等的痛苦，甚至导致死亡。乳腺癌骨转移的发病机制非常复杂，与乳腺癌细胞以及发生骨转移的骨骼都有关联。目前普遍为人接受的理论是骨的微环境为癌细胞的生长提供了适宜的环境以及肿瘤细胞中骨转移相关细胞因子的推动。因此，对于乳腺癌骨转移尚未有明确的预防治疗手段，而临床常用的治疗手段为全身化疗以及使用骨改良药物双膦酸盐，但是治疗效果并不理想，并且化疗对于患者身体健康损害巨大。因此，对于乳腺癌骨转移的研究的重点更多的转移到早期防治上。
meso-Hannokinol，化学名1,7-双-(4-羟苯基)-3,5-庚二醇，结构式如下：
其是从中药材莪术当中分离出的一种天然产物，目前尚未见关于meso-Hannokinol功能的报道。
发明内容
发明目的：针对上述莪术功效，本申请提供了莪术提取物meso-Hannokinol在制备治疗乳腺癌骨转移的药物中的应用。
本发明的目的可通过以下技术方案实现：
莪术提取物meso-Hannokinol在制备治疗乳腺癌转移的药物中的应用。
作为本发明的一种优选，莪术提取物meso-Hannokinol在制备治疗乳腺癌骨转移的药物中的应用。
进一步的，莪术提取物meso-Hannokinol在制备降低乳腺癌细胞的迁移能力从而预防乳腺癌骨转移发生的药物中的应用。
进一步的，莪术提取物meso-Hannokinol在制备通过降低乳腺癌造成的骨溶解和骨破坏来减少乳腺癌骨转移造成的骨损伤的药物中的应用。
进一步的，所述莪术提取物meso-Hannokinol有效抑制了裸鼠体内乳腺癌细胞的骨转移。有益效果：本申请通过实验验证莪术提取物meso-Hannokinol能够降低乳腺癌细胞的迁移能力从而预防骨转移的发生；能够降低乳腺癌造成的骨溶解和骨破坏来减少乳腺癌骨转移造成的骨损伤；能够有效抑制了裸鼠体内乳腺癌细胞的骨转移，从而莪术提取物meso-Hannokinol可用于开发抗乳腺癌骨转移的相关药物。
附图说明
图1为伤口愈合实验及其定量分析meso-Hannokinol对乳腺癌高骨转移细胞MDA-MB-231BO转移能力的影响；
图2为Transwell实验及其定量分析meso-Hannokinol对乳腺癌高骨转移细胞MDA-MB-231BO转移能力的影响；
图3为Trap定量分析meso-Hannokinol对乳腺癌高骨转移细胞MDA-MB-231BO的条件培养基诱导的巨噬细胞RAW264.7细胞破骨分化的影响；
图4为小动物活体成像及其定量分析meso-Hannokinol对裸鼠体内乳腺癌骨转移的影响。
具体实施方式
下面结合具体实施例对本申请做出详细说明
实施例所用meso-Hannokinol由申请人实验室分离提取获得，并经结构确认。
实施例所用高骨转移细胞MDA-MB-231BO由申请人构建获得，构建方法详见专利CN111593026A。
实施例1 meso-Hannokinol在划痕实验中抑制了乳腺癌高骨转移细胞MDA-MB-231BO的转移
取对数生长期的MDA-MB-231BO细胞，用胰酶消化离心后，完全培养基重悬细胞，利用细胞计数仪调整细胞数为3×105cells/ml，接种到6孔板中，每孔2ml，放入培养箱中培养。用200微升移液枪头在细胞表面划出一道垂直的划痕，随后用PBS荡洗细胞2次，以去除划下的残余细胞，加入含不同浓度的meso-Hannokinol无血清培养基培养，继续培养24h待细胞贴壁后，在显微镜下观察药物处理0h、24h细胞迁移的变化并拍照，并计算划痕愈合率＝(0h划痕宽度-24h划痕宽度)/0h划痕宽度×100％，以此反应细胞迁移能力。
结果如图1所示，meso-Hannokinol显著降低了划痕的愈合，表明meso-Hannokinol能够显著降低MDA-MB-231BO的迁移能力。
实施例2 meso-Hannokinol在Transwell实验中抑制了乳腺癌高骨转移细胞MDA-MB-231BO的转移
将MDA-MB-231BO细胞以3万/孔铺入transwell板的上层小室中，并使用含不同浓度meso-Hannokinol无血清培养基培养，同时在transwell板的下层小室中加入含10％血清的培养基用于诱导肿瘤细胞的迁移，培养24小时后，将小室取出使用PBS清洗两遍后，将小室放入多聚甲醛固定液中固定30分钟，再次使用PBS清洗两边，将小室放入结晶紫染色液中将细胞染色30分钟，再次使用PBS清洗后使用棉签轻轻擦除小室薄膜上层未迁移的细胞，在显微镜下拍摄小室薄膜下层发生迁移的细胞，随机选取5个视野，计数迁移细胞数目，通过迁移细胞数目反应细胞迁移能力。
结果如图2所示，meso-Hannokinol能够呈剂量依赖性的降低细胞迁移数目，表明meso-Hannokinol能够显著降低MDA-MB-231BO的迁移能力。
实施例3 meso-Hannokinol抑制乳腺癌高骨转移细胞MDA-MB-231BO的条件培养基诱导的巨噬细胞RAW264.7细胞破骨分化
收集乳腺癌高骨转移细胞MDA-MB-231BO的培养基，使用0.22μm水相滤膜过滤后，按照1：1比例与含10％血清培养基混合得到乳腺癌高骨转移细胞MDA-MB-231BO的条件培养基(CM)。将RAW264.7以10万/孔铺入12孔板中，分别用普通培养基，条件培养基，含meso-Hannokinol(50μM)的条件培养基培养RAW264.7细胞48h，使用碧云天公司生产的抗酒石酸酸性磷酸酶检测试剂盒检测RAW264.7细胞中抗酒石酸酸性磷酸酶(TRAP)水平。抗酒石酸酸性磷酸酶是一种糖基化的含金属蛋白酶，被认为是机体破骨活性的重要指标。
结果如图3所示，条件培养基培养能够大幅升高细胞内TRAP水平，表明乳腺癌高骨转移细胞MDA-MB-231BO的条件培养基能够诱导巨噬细胞的破骨分化，而meso-Hannokinol则可以显著降低条件培养基造成的破骨分化，使其TRAP水平降低。表明meso-Hannokinol抑制乳腺癌高骨转移细胞MDA-MB-231BO的条件培养基诱导的巨噬细胞RAW264.7细胞破骨分化。
实施例4
1.裸鼠体内乳腺癌骨转移模型的建立
所有的动物实验程序均符合中国药科大学动物伦理委员会的批准。从上海必凯购买六周龄雌性Balb/c裸鼠24只，自由饮水适应性饲养一周后对21只裸鼠进行乳腺癌骨转移造模，具体方案：收集乳腺癌MDA-MB-231BO细胞使其浓度为1000万/ml，将细胞置于冰上保持活力，将裸鼠麻醉后，麻醉后呈仰卧位,消毒裸鼠腹面皮肤,使用29G胰岛素注射器吸取100μl细胞悬液将肿瘤细胞注射入裸鼠左心室，每只鼠接种量为100万个细胞，进针角度与裸鼠腹面正中线呈45°,与皮肤呈30°,进针深度约为0.8cm。当见到红色细柱状血液缓缓进入针筒时,说明针尖已经在裸鼠左心室,此时慢慢推注肿瘤细胞悬液,速度为0.1mL/min。注射完毕后消毒裸鼠皮肤,将裸鼠放回笼中。裸鼠左心室注射建模后隔天称重，体质量低于16g时严密观察。
2.给药方案和试验方法
造模后死亡三只，将剩余18只裸鼠随机分为三组，分别为：模型组，meso-Hannokinol(HA)低剂量组(25mg/kg),meso-Hannokinol(HA)高剂量组(50mg/kg),每组六只。Meso-Hannokinol使用5％DMSO+15％PEG400+5％吐温-80+75％生理盐水的配比溶解，腹腔注射meso-Hannokinol溶液200μL，两天一次，连续注射两周，模型组注射相同体积的溶剂。给药两周后，取出裸鼠麻醉后，注射活体成像试剂D-荧光素，15分钟后，使用MaestroTM小动物活体成像仪拍摄裸鼠体内荧光分布情况。
结果如图4所示，模型组的裸鼠腿骨部位积聚了大量乳腺癌细胞，而HA低剂量组(25mg/kg),HA高剂量组(50mg/kg)的裸鼠腿骨部位荧光强度降低，表明转移至腿骨部位的乳腺癌细胞更少，meso-Hannokinol可以显著抑制乳腺癌骨转移。
Claims (4)
1.莪术提取物meso-Hannokinol在制备治疗乳腺癌转移的药物中的应用。
2.根据权利要求1所述的应用，其特征在于莪术提取物meso-Hannokinol在制备治疗乳腺癌骨转移的药物中的应用。
3.根据权利要求2所述应用，其特征在于莪术提取物meso-Hannokinol在制备降低乳腺癌细胞的迁移能力从而预防乳腺癌骨转移发生的药物中的应用。
4.根据权利要求2所述应用，其特征在于莪术提取物meso-Hannokinol在制备通过降低乳腺癌造成的骨溶解和骨破坏来减少乳腺癌骨转移造成的骨损伤的药物中的应用。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107124883A (zh) * | 2014-07-31 | 2017-09-01 | 凯尔格恩有限公司 | 具有破骨细胞分化及活性抑制能力的肽及其用途 |
| TW201806589A (zh) * | 2016-08-15 | 2018-03-01 | 中國醫藥大學 | 用於治療骨質疏鬆之醫藥組合物 |
| CN109674742A (zh) * | 2019-03-07 | 2019-04-26 | 康赋葆(深圳)生物医药科技有限公司 | 一种姜黄素类亲水凝胶骨架缓释组合物、制备方法及其在抗癌领域的应用 |
| CN111593026A (zh) * | 2020-07-08 | 2020-08-28 | 上海市东方医院（同济大学附属东方医院） | 一种荧光标记的人三阴性乳腺癌骨转移细胞株 |
-
2021
- 2021-11-08 CN CN202111311392.XA patent/CN113786397B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107124883A (zh) * | 2014-07-31 | 2017-09-01 | 凯尔格恩有限公司 | 具有破骨细胞分化及活性抑制能力的肽及其用途 |
| TW201806589A (zh) * | 2016-08-15 | 2018-03-01 | 中國醫藥大學 | 用於治療骨質疏鬆之醫藥組合物 |
| CN109674742A (zh) * | 2019-03-07 | 2019-04-26 | 康赋葆(深圳)生物医药科技有限公司 | 一种姜黄素类亲水凝胶骨架缓释组合物、制备方法及其在抗癌领域的应用 |
| CN111593026A (zh) * | 2020-07-08 | 2020-08-28 | 上海市东方医院（同济大学附属东方医院） | 一种荧光标记的人三阴性乳腺癌骨转移细胞株 |
Non-Patent Citations (6)
| Title |
|---|
| ANA GALLEGO等: "Viability-reducing activity of Coryllus avellana L. extracts against human cancer cell lines", 《BIOMEDICINE & PHARMACOTHERAPY》 * |
| ANA GALLEGO等: "Viability-reducing activity of Coryllus avellana L. extracts against human cancer cell lines", 《BIOMEDICINE & PHARMACOTHERAPY》, 31 December 2017 (2017-12-31), pages 565 - 572 * |
| LAURA E. WRIGHT等: "Curcuminoids Block TGF-β Signaling in Human Breast Cancer Cells and Limit Osteolysis in a Murine Model of Breast Cancer Bone Metastasis", 《JOURNAL OF NATURAL PRODUCTS》 * |
| LAURA E. WRIGHT等: "Curcuminoids Block TGF-β Signaling in Human Breast Cancer Cells and Limit Osteolysis in a Murine Model of Breast Cancer Bone Metastasis", 《JOURNAL OF NATURAL PRODUCTS》, 12 November 2012 (2012-11-12), pages 316 - 321 * |
| 张敏等: "四氢姜黄素对MCF-7细胞增殖、凋亡及转移的作用", 《中成药》 * |
| 张敏等: "四氢姜黄素对MCF-7细胞增殖、凋亡及转移的作用", 《中成药》, vol. 44, no. 3, 30 March 2021 (2021-03-30), pages 942 - 947 * |
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