摘要
目的研究甲磺酸阿帕替尼、小檗碱及两药联合对Hep-G2细胞增殖、周期分布、凋亡的影响,探讨其抗肿瘤机制。方法 CCK-8法检测甲磺酸阿帕替尼、小檗碱及两药联合对Hep-G2细胞增殖的抑制作用;流式细胞术检测甲磺酸阿帕替尼、小檗碱及两药联合对细胞周期分布、细胞凋亡的影响。结果甲磺酸阿帕替尼及小檗碱对Hep-G2细胞均具有增殖抑制作用,且呈现浓度、时间依赖性;其25%抑制浓度(IC25)值分别为0.5,30μmol·L^-1;两药联合时,Hep-G2的增殖抑制率也呈时间依赖性(P<0.05);甲磺酸阿帕替尼干预Hep-G2后G0/G1期细胞增加,S期及G2/M期细胞减少,小檗碱干预Hep-G2后G2/M期细胞增加,G0/G1期及S期细胞减少,两药联合干预后G0/G1期细胞明显增加,S期及G2/M期细胞减少(P<0.01);甲磺酸阿帕替尼、小檗碱干预Hep-G2细胞均可促进细胞凋亡,凋亡率与药物作用时间呈正相关,两药联合时,细胞凋亡率进一步提高(P<0.05)。甲磺酸阿帕替尼、小檗碱均可抑制Hep-G2细胞增殖,且呈时间-浓度依赖性,当两药联合时其增殖抑制作用进一步加强,呈现出时间依赖性。结论甲磺酸阿帕替尼、小檗碱均可阻滞细胞周期、促进细胞凋亡,且均呈现时间依赖性,两药联合时效果更明显。
Objective To study the effects of apatinib mesylate, berberine and combination two drugs on the proliferation, cell cycle distribution and apoptosis of Hep-G2 cells, and to explore the mechanism. Methods CCK-8 method was used to detect the inhibitory effect of the treatments;Cell cycle distribution and apoptosis were detected by flow cytometry. Results Apatinib mesylate and berberine had a certain inhibitory effect on the proliferation of Hep-G2 cells, and both showed a concentration and time dependence manner;their IC25 values were 0.5 μmol·L-1 and 30 μmol·L-1, respectively.When the two drugs were combined, the proliferation inhibition rate of Hep-G2 was also time-dependent after apatinib mesylate treatment, the proportion of cells in G0/G1 phase increased, and the proportion of cells in S phase and G2/M phase decreased.After berberine treatment, the proportion of cells in G2/M phase increased, and the proportion of cells in G0/G1 phase and S phase decreased when combined two drugs to treat Hep-G2 cells, the proportion of cells in G0/G1 phase increased significantly, while the proportion of cells in S phase and G2/M phase decreased(P<0.01);Both of apatinib mesylate and berberine could induce apoptosis in Hep-G2 cells in a time-dependent manner;And the rate of apoptosis was further enhanced by the combination use of two drugs(P<0.05).Both apatinib mesylate and berberine inhibited the proliferation of Hep-G2 cells in a time-concentration dependent manner, and the proliferation inhibition was further strengthened when the two drugs were combined, which also showed a time-dependent effect. Conclusion Apatinib mesylate and berberine can both cause cell cycle arrest and promote apoptosis in a time-dependent manner, and the effect is more obvious when the two drugs are combined.
作者
谢俊杰
邓波
易峰涛
邵志雄
徐振华
XIE Junjie;DENG Bo;YI Fengtao;SHAO Zhixiong;XU Zhenhua(Department of Radiotherapy, GeneralHospital of Central Theater Command of Chinese People's Liberation Army, Wuhan 430070, China;Center of Cancer, Xianning Central Hospital, Hubei Province,Xianning 437000, China)
出处
《医药导报》
CAS
北大核心
2019年第11期1414-1418,共5页
Herald of Medicine
基金
中国博士后自然科学基金资助项目(2013M542581)
关键词
甲磺酸阿帕替尼
小檗碱
肝癌
细胞增殖
细胞周期
细胞凋亡
Apatinib,mesylate
Berberine
Hepatocellular carcinoma
Cell proliferation
Cell cycle
Apoptosis
