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组蛋白去乙酰化酶抑制剂MGCD0103可导致肝癌细胞的细胞周期阻滞、凋亡和自噬。

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

作者信息

Liao Bo, Sun Quan, Yuan Yufeng, Yin Yuchun, Qiao Jianguo, Jiang Ping

机构信息

Department of Hepatopancreatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

J Cancer. 2020 Jan 29;11(7):1915-1926. doi: 10.7150/jca.34091. eCollection 2020.

DOI:10.7150/jca.34091
PMID:32194803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7052879/
Abstract

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. 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. Cell viability and colony formation assays showed that MGCD0103 inhibited the proliferation of liver cancer cells . 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. MGCD0103 suppressed the growth of liver cancer cells and . It could serve as a novel therapeutic approach for liver cancer.

摘要

肝癌是全球癌症相关死亡的常见原因。MGCD0103是一种组蛋白脱乙酰酶抑制剂，对多种癌症具有抗肿瘤作用。然而，其在肝癌中的作用仍不清楚。通过细胞活力测定、集落形成测定、细胞周期分析、凋亡分析、活性氧（ROS）测定、蛋白质印迹、免疫组织化学和异种移植测定等多项实验验证了MGCD0103对HepG2和Huh7细胞的作用。细胞活力和集落形成测定表明MGCD0103抑制肝癌细胞的增殖。流式细胞术和蛋白质印迹分析表明MGCD0103诱导G2/M期阻滞和线粒体相关凋亡。泛半胱天冬酶抑制剂和ROS清除剂抑制MGCD0103诱导的凋亡。此外，MGCD0103导致与细胞死亡相关的自噬，自噬抑制剂抑制MGCD0103诱导的凋亡和自噬。最终，MGCD0103在动物模型中减弱了肿瘤生长，但未显示出明显的全身毒性。MGCD0103抑制肝癌细胞的生长。它可作为肝癌的一种新型治疗方法。

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