李淑群, 陈谦, 廖维甲, 翁俊, 莫庆荣, 李菁玲, 喻亚群. 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[J]. 中国肿瘤临床, 2017, 44(15): 750-754. DOI: 10.3969/j.issn.1000-8179.2017.15.136
引用本文: 李淑群, 陈谦, 廖维甲, 翁俊, 莫庆荣, 李菁玲, 喻亚群. 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[J]. 中国肿瘤临床, 2017, 44(15): 750-754. DOI: 10.3969/j.issn.1000-8179.2017.15.136
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LI Shuqun, CHEN Qian, LIAO Weijia, WENG Jun, MO Qingrong, Li Jingling, YU Yaqun. A new mitochondria-targeted platinum complex Mor-platin inhibits HepG2 cell proliferation and cell invasion[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2017, 44(15): 750-754. DOI: 10.3969/j.issn.1000-8179.2017.15.136
Citation: LI Shuqun, CHEN Qian, LIAO Weijia, WENG Jun, MO Qingrong, Li Jingling, YU Yaqun. A new mitochondria-targeted platinum complex Mor-platin inhibits HepG2 cell proliferation and cell invasion[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2017, 44(15): 750-754. DOI: 10.3969/j.issn.1000-8179.2017.15.136
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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

    摘要
  • 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(IC50)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:
      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 (IC50) 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.

     

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