组蛋白去乙酰化酶抑制剂对肝癌诱导自噬的作用

doi:10.3969/j.issn.1000-8535.2022.02.009

摘要/Abstract

摘要： 目的探讨组蛋白去乙酰化酶抑制剂曲古霉素对肝癌细胞增殖凋亡是否存在影响,及该抑制作用是否与自噬相关。方法采用MTT法检测不同浓度曲古霉素作用于肝癌HepG2细胞24 h、48 h、72 h以后肝癌细胞的增殖能力;使用流式细胞术检测不同浓度曲古霉素对HepG2肝癌细胞周期及凋亡的影响;蛋白印迹法(Western blot, WB)检测不同浓度曲古霉素对肝癌HepG2细胞中Beclin1和Bcl-2蛋白的表达;实时荧光定量 PCR(Real-time PCR, RT-PCR)检测不同浓度曲古霉素对肝癌HepG2细胞中Beclin1和Bcl-2 mRNA的表达。结果曲古霉素对肝癌HepG2细胞具有增殖抑制作用,与对照组相比较,其差异有统计学意义(P＜0.05);通过流式细胞术检测结果显示,曲古霉素作用于肝癌HepG2细胞后,随着浓度的增加,细胞凋亡率显著上升,与对照组相比,差异有统计学意义(P＜0.05);RT-PCR及WB实验观察到,Beclin1蛋白和mMRA的表达随着曲古霉素浓度的增加而逐渐升高,Bcl-2蛋白和mMRA的表达随着曲古霉素作用浓度的增加而逐渐降低,且与对照组相比,其差异均有统计学意义(P＜0.05)。结论曲古霉素能抑制肝癌细胞的增殖,而且这种作用机制与诱导肝癌细胞凋亡和自噬作用有相关性。

关键词: 肝癌, 曲古霉素, 凋亡, 自噬

Abstract: Objective To investigate whether histone deacetylase inhibitor hachimycin has an effect on the proliferation and apoptosis of hepatocellular carcinoma cells and whether the inhibition is related to autophagy. Methods MTT assay was used to detect the proliferation ability of HepG2 cells treated with hachimycin of different concentrations for 24 h, 48 h and 72 h.Flow cytometry was used to detect the effects of different concentrations of hachimycin on HepG2 hepatoma cell cycle and apoptosis.Western blot (WB) assay was used to detect Beclin1 and Bcl-2 expressions in hepatocellular carcinoma HepG2 cells under different hachimycin concentrations.Beclin1 and Bcl-2 mRNA expressions under different hachimycin concentrations in hepatocellular carcinoma HepG2 cells were detected by RT-PCR. Results Hachimycin inhibited the proliferation of HepG2 cells, compared with the control group, the difference was statistically significant (P<0.05). Flow cytometry results showed that the apoptosis rate of hepatocellular carcinoma HepG2 cells was significantly increased with the increase of hachimycin concentration, compared with the control group, the difference was statistically significant (P<0.05). RT-PCR and WB results showed that Beclin1 protein and mMRA expression gradually increased with the increase of hachimycin concentration, while Bcl-2 protein and mMRA expression gradually decreased, compared with the control group, the differences were statistically significant (P<0.05). Conclusion Hachimycin could inhibit the proliferation of hepatocellular carcinoma cells, and its mechanism was related to the induction of apoptosis and autophagy.

Key words: hepatocellular carcinoma, hachimycin, apoptosis, autophagy

庄薇, 钟宁. 组蛋白去乙酰化酶抑制剂对肝癌诱导自噬的作用[J]. 广州医药, 2022, 53(2): 39-43.

ZHUANG Wei, ZHONG Ning. Effect of histone deacetylase inhibitors on hepatocellular carcinoma induced autophagy[J]. Guangzhou Medical Journal, 2022, 53(2): 39-43.

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