Histone deacetylase inhibitor MGCD0103 causes cell cycle arrest, apoptosis, and autophagy in liver cancer cells

被引:21
作者
Liao, Bo [1 ]
Sun, Quan [1 ]
Yuan, Yufeng [1 ]
Yin, Yuchun [1 ]
Qiao, Jianguo [1 ]
Jiang, Ping [1 ]
机构
[1] Wuhan Univ, Zhongnan Hosp, Dept Hepatopancreatobiliary Surg, 169 Donghu Rd, Wuhan 430071, Peoples R China
关键词
liver cancer; MGCD0103; cell growth; cell cycle arrest; apoptosis; autophagy; S-PHASE ARREST; HEPATOCELLULAR-CARCINOMA; THERAPY;
D O I
10.7150/jca.34091
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: Liver cancer is a common cause of cancer-related death all over the world. MGCD0103, a histone deacetylase inhibitor, exerts antitumor effect on various cancers. However, its role in liver cancer remains unclear. Methods: The effect of MGCD0103 on HepG2 and Huh7 cells was verified by several experiments such as cell viability assay, colony formation assay, cell cycle analysis, apoptosis analysis, reactive oxygen species (ROS) assay, western blotting, immunohistochemistry, and xenograft assay. Results: Cell viability and colony formation assays showed that MGCD0103 inhibited the proliferation of liver cancer cells in vitro. Flow cytometry and western blotting analysis demonstrated that MGCD0103 induced G2/M phase arrest and mitochondrial-related apoptosis. A pan-caspase inhibitor and ROS scavenger inhibited apoptosis induced by MGCD0103. What's more, MGCD0103 led to autophagy associated with cell death and an autophagy inhibitor inhibited apoptosis and autophagy induced by MGCD0103. Ultimately, MGCD0103 attenuated tumor growth but did not show significant systemic toxicity in animal model. Conclusions: MGCD0103 suppressed the growth of liver cancer cells in vitro and in vivo. It could serve as a novel therapeutic approach for liver cancer.
引用
收藏
页码:1915 / 1926
页数:12
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