| 寇 丹,杨兴祥,刘 冰,孙 宏,刘仁伟,林 剑,蒋 奕,彭思璐.BIX-01294对肝癌细胞周期、凋亡及移植瘤的影响[J].现代生物医学进展英文版,2021,(4):634-638. |
| BIX-01294对肝癌细胞周期、凋亡及移植瘤的影响 |
| Effect of BIX-01294 on Cell Cycle, Apoptosis and Transplanted Tumor of Hepatocarcinoma |
| Received:September 06, 2020 Revised:September 30, 2020 |
| DOI：10.13241/j.cnki.pmb.2021.04.007 |
| 中文关键词: 组蛋白甲基转移酶 肝癌 增殖 凋亡 BIX-01294 |
| 英文关键词: Histone methyl transferase Liver cancer Proliferation Apoptosis BIX-01294 |
| 基金项目:国家卫生计生委医药卫生科技发展研究中心项目（W2014HB240）；四川省卫生和计划生育委员会基金项目（18PJ342） |
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| 中文摘要: |
| 摘要 目的：探究组蛋白甲基转移酶G9a抑制剂（BIX-01294）对肝癌细胞周期、凋亡及移植瘤的影响。方法：将SMMC-7721、BEL-7402、HL-7702原始细胞株传代培养后，分为空白对照组和不同浓度（1 μM、5 μM、10 μM、20 μM）BIX-01294处理组。应用Western-blot法检测G9a及肝癌细胞内凋亡蛋白CC3、C-PARP、 Bax、Bcl-2表达水平；应用四甲基偶氮唑盐（MTT）比色法检测不同浓度BIX-01294 处理SMMC-7721、BEL-7402细胞24、48、72、96 h后的细胞增殖情况；应用流式细胞术检测不同浓度的BIX-01294处理肝癌细胞96h后细胞周期分布情况；移植瘤试验21 d后测量裸鼠体内肿瘤体积及重量，并检测瘤体内H3K9me2的蛋白水平。结果：G9a 在肝癌细胞SMMC-7721、BEL-7402中表达水平高于HL-7702细胞（P<0.05）。不同浓度的BIX-01294对SMMC-7721细胞和BEL-7402细胞增殖具有抑制作用，且具有时间依赖性和剂量依赖性（均P<0.05）。不同浓度BIX-01294处理细胞96h后，SMMC-7721细胞和BEL-7402细胞G0/G1期细胞比例增加，S和G2/M期的细胞比例降低(P<0.05)。5 μM BIX-01294处理细胞96h后能明显增加CC3、Bax、C-PARP表达水平，并降低Bcl-2的表达水平(P<0.05)，与空白对照组相比，BIX-01294处理组裸鼠肿瘤体积减小，重量较低，且肿瘤组织内H3K9me2的表达水平下降(P<0.05)。结论：BIX-01294导致SMMC-7721、BEL-7402细胞发生周期阻滞和凋亡，且对肿瘤的生长具有明显的抑制作用，其可能是通过抑制G9a的表达从而降低H3K9me2的表达来抑制肿瘤的生长。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of Inhibitors of protein methyltransferase G9a （BIX-01294）on the cell cycle, apoptosis and transplanted tumor. Methods: SMMC-7721, BEL-7402, HL-7702 cell lines were subcultured and divided into blank control group and BIX-01294 treatment group with different concentrations(1 μM, 5 μM，10 μM，20 μM). Western blot was used to detect the expression level of G9a and apoptosis protein CC3, C-PARP, Bax, Bcl-2. The proliferation of SMMC-7721 and BEL-7402 cells treated with BIX-01294 at different concentrations for 24, 48, 72 and 96 hours was detected by Tetramethylazozolium salt(MTT) colorimetry; the cell cycle distribution of hepatoma cells treated with different concentrations of BIX-01294 for 96 hours were examined by flow cytometry; the tumor volume, weight, the protein level of H3K9me2 were measured 21 days after tumor transplantation experiment in nude mice. Results: The expression level of G9a in SMMC-7721 and BEL-7402 cell were higher than HL-7702 cell(P<0.05). Various concentrations of BIX-01294 could inhibit SMMC-7721 cell and BEL-7402 cell proliferation in a time-dependent and dose-dependent manner (P<0.05). There is a significant difference in cell cycle distribution with increased G0/G1 phage cell percentage, reduced S and G2/M phage cell percentage at 96h by BIX-01294 treated (P<0.05). The expression levels of CC3, Bax, C-PARP were significantly increased, and the Bcl-2 level were significantly reduced at 96 h by 5 μM BIX-01294 treated (P<0.05). Compared with the blank control group, the tumor volume and weight of the bix-01294 treated group decreased, and the expression level of H3K9me2 in tumor tissue decreased(P<0.05). Conclusion: BIX-01294 leads to cell cycle arrest and apoptosis of SMMC-7721 and BEL-7402 cells, and has a significant inhibitory effect on tumor growth. It may be through inhibiting the expression of G9a to reduce the expression of H3K9me2 to inhibit tumor growth. |
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