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

A new mitochondria-targeted platinum complex Mor-platin inhibits HepG2 cell proliferation and cell invasion

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。

Objective：To investigate the effects of Mor-platin,a novel mitochondrial platinum complex,on proliferation and migration of human hepatoma carcinoma HepG2 cells.Methods：Cell counting kit-8（CCK-8） assay was used to analyze cell proliferation of Morplatin and classic anticancer drugs,particularly cisplatin,in HepG2 cells.A laser confocal microscope was used to observe whether Mor-platin can target mitochondria.The morphological changes in cellular mitochondria after treatment with Mor-platin were observed on a transmission electron microscope.Cell apoptosis was measured by flow cytometry,and cell invasion was evaluated by three-dimensional tumor spheroid model.Results：Mor-platin can inhibit cell proliferation and is dose dependent.The half inhibitory concentration（IC_（50）） of Mor-platin is lower than that of cisplatin.Laser confocal images showed that Mor-platin can target cell mitochondria and enrich cell mitochondria.Transmission electron microscopy images showed that cell mitochondrial morphology changed after Mor-platin treatment.Furthermore,cell mitochondrial membrane is incomplete and mitochondrial cristae are reduced.Cell apoptosis caused by Mor-platin is dose dependent.The three-dimensional tumor spheroid model showed that the cell areas of the group subjected to Mor-platin treatment are smaller than those of the control group.Conclusion：Mor-platin can target cell mitochondria,change the cell mitochondrial morphology,inhibit cell proliferation,and thus promote cell apoptosis.It also showed better anticancer effects than cisplatin.Furthermore,Mor-platin can inhibit three-dimensional tumor spheroid invasion.These results suggest that Mor-platin is a potential antitumor drug.