华蟾毒配基抑制组蛋白乙酰化诱导肝癌细胞死亡的机制

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Abstract Objective To investigate the mechanism of cinobufagin in regulating the death of liver cells by regulating epigenetic modification. Methods The CCK-8 assay was used to detect the changes of proliferation ability after different concentrations (0, 0.75, 1.5, 2.5, 5, 10 μmol/L) of cinobufagin acting on the HepG2 cells for 24 h; after 5 μmol/L of cinobufagin acting on the HepG2 cells for 12, 24 h, the cell cycle was detected by flow cytometry, and the expression levels of Ca2+/Calmodulin-dependent protein kinase 2β (CaMK2B), methylated-cpg binding protein (MeCP2), phosphorylation-MeCP2 (p-MeCP2), acetylated histone H3.1 (Ac-Histone3.1) and methylated histones (Met-Histone3.1) were detected by Western blot; after 5 μmol/L of cinobufagin acting on the HepG2 cells for 24 h, the interaction between CaMK2B and MeCP2 in HepG2 cells was detected by cell immunofluorescence combined with confocal scanning. Results Cinobufagin could inhibit the growth of HepG2 cells in a dose-independent manner, the difference was statistically significant (P ＜ 0.05), after the drug acting on the cells, the cell cycle comes up G2/M phase arrest, the difference was statistically significant (P ＜ 0.05). 5 μmol/L of cinobufagin could promote the incorporation of CaMK2B and MeCP2 in cell nucleus, the results of Western blot showed that the cinobufagin could increase the expression of CaMK2B and MeCP2 after acting on HepG2 cells (P ＜ 0.05), inhibit the expression of the Ac-Histone3.1, and promote the Met-Histone3.1 (P ＜ 0.05). Conclusion Cinobufagin can induce the death of liver cells by activating the CaMK2B-MeCP2 signal path, inhibiting histone acetylation and promoting histone methylation.

Key words： Cinobufagin Hepatocellular carcinoma Calmodulin kinase Epigenetic

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	BI Cheng1 XU Ruicheng2 ZOU Shuang2 WANG Congcong2 ZHANG Yan2 XU Zhongwei2

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BI Cheng1 XU Ruicheng2 ZOU Shuang2 WANG Congcong2 ZHANG Yan2 XU Zhongwei2. The mechanism of cinobufagin in inducing the death of liver cells by inhibition of histone acetylation[J]. 中国医药导报, 2018, 15(23): 4-8.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2018/V15/I23/4

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