新型线粒体靶向铂类配合物Mor-platin抑制肝癌细胞HepG2增殖和抑制细胞球侵袭的研究
发布时间：2018-08-11 15:56
【摘要】：目的:探讨新型线粒体靶向性铂类配合物Mor-platin对人肝癌细胞HepG2的细胞增殖和细胞球侵袭的影响。方法:运用细胞毒性实验CCK-8法,比较新型线粒体靶向性铂类配合物Mor-platin和经典铂类抗癌药顺铂(cisplatin)对人肝癌细胞HepG2的细胞增殖抑制作用;利用激光共聚焦显微镜观察Mor-platin是否靶向于线粒体;利用透射电子显微镜观察Mor-platin对细胞线粒体形态的影响;流式细胞仪检测Mor-platin作用细胞后细胞凋亡的改变;建立三维肿瘤细胞球模型,探讨Mor-platin对细胞球侵袭的影响。结果:Mor-platin能够抑制HepG2细胞增殖,半数抑制浓度(IC_(50))少于cisplatin;Mor-platin能够靶向到线粒体;加Mor-platin后,细胞线粒体膜结构不完整,嵴不清晰或消失以及线粒体中有大片空白区域;Mor-platin引起的细胞凋亡具有剂量依赖性;三维肿瘤细胞球模型显示,Mor-platin处理的细胞球面积小于对照组。结论:新型线粒体靶向性铂配合物Mor-platin能够靶向于细胞的线粒体,引起线粒体形态变化,抑制细胞增殖,最终导致细胞凋亡,Mor-platin还能抑制三维肿瘤细胞球侵袭,比cisplatin具有更好的抗癌效果。上述研究结果提示Mor-platin具有成为新抗肿瘤药物的潜质。
[Abstract]:Aim: to investigate the effects of a novel mitochondrial targeted platinum complex (Mor-platin) on the proliferation and cell ball invasion of human hepatoma cell line HepG2. Methods: cytotoxicity assay (CCK-8) was used to compare the inhibitory effects of a novel mitochondrial targeted platinum complex (Mor-platin) and a classical platinum anticancer agent (cisplatin (cisplatin) on the proliferation of human hepatoma cell line HepG2. Laser confocal microscopy was used to observe whether Mor-platin was targeted on mitochondria, transmission electron microscope was used to observe the effect of Mor-platin on the morphology of mitochondria, flow cytometry was used to detect the changes of cell apoptosis after Mor-platin treatment. Three-dimensional tumor cell ball model was established to investigate the effect of Mor-platin on cell ball invasion. Results the proliferation of HepG2 cells was inhibited by the addition of Mor-platin, and the half inhibitory concentration (IC50) was less than that of cisplatin Mor-platin targeting mitochondria, and the membrane structure of mitochondria was incomplete after addition of Mor-platin. The apoptosis induced by Mor-platin in mitochondria was dose-dependent, and the area of cells treated with Mor-platin was smaller than that of control group. Conclusion: Mor-platin, a novel mitochondrial targeted platinum complex, can target the mitochondria, induce mitochondrial morphological changes, inhibit cell proliferation, and eventually lead to apoptosis. Mor-platin can also inhibit the invasion of three-dimensional tumor cells. It has better anti-cancer effect than cisplatin. These results suggest that Mor-platin has the potential to be a new anti-tumor drug.
【作者单位】： 桂林医学院附属医院肝胆胰外科;苏州大学附属儿童医院病案统计室;
【基金】：国家自然科学基金项目(编号:81372163) 广西省自然科学基金项目(编号:2015GXNSFAA139111)资助~~
【分类号】：R730.5
本文编号：2177464
[Abstract]:Aim: to investigate the effects of a novel mitochondrial targeted platinum complex (Mor-platin) on the proliferation and cell ball invasion of human hepatoma cell line HepG2. Methods: cytotoxicity assay (CCK-8) was used to compare the inhibitory effects of a novel mitochondrial targeted platinum complex (Mor-platin) and a classical platinum anticancer agent (cisplatin (cisplatin) on the proliferation of human hepatoma cell line HepG2. Laser confocal microscopy was used to observe whether Mor-platin was targeted on mitochondria, transmission electron microscope was used to observe the effect of Mor-platin on the morphology of mitochondria, flow cytometry was used to detect the changes of cell apoptosis after Mor-platin treatment. Three-dimensional tumor cell ball model was established to investigate the effect of Mor-platin on cell ball invasion. Results the proliferation of HepG2 cells was inhibited by the addition of Mor-platin, and the half inhibitory concentration (IC50) was less than that of cisplatin Mor-platin targeting mitochondria, and the membrane structure of mitochondria was incomplete after addition of Mor-platin. The apoptosis induced by Mor-platin in mitochondria was dose-dependent, and the area of cells treated with Mor-platin was smaller than that of control group. Conclusion: Mor-platin, a novel mitochondrial targeted platinum complex, can target the mitochondria, induce mitochondrial morphological changes, inhibit cell proliferation, and eventually lead to apoptosis. Mor-platin can also inhibit the invasion of three-dimensional tumor cells. It has better anti-cancer effect than cisplatin. These results suggest that Mor-platin has the potential to be a new anti-tumor drug.
【作者单位】： 桂林医学院附属医院肝胆胰外科;苏州大学附属儿童医院病案统计室;
【基金】：国家自然科学基金项目(编号:81372163) 广西省自然科学基金项目(编号:2015GXNSFAA139111)资助~~
【分类号】：R730.5
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1 许德晨;铂类配合物的抗癌作用机理的研究[D];中国科学技术大学;2014年
2 张金超;新型铂（Ⅱ）类配合物的合成、表征和抗肿瘤活性的研究[D];浙江大学;2000年
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