蔡爽,韩冰,郑璐,汤雷,马子华,陈雨丝,杨婷,杨勤,谢汝佳
CAI Shuang,HAN Bing,ZHENG Lu,TANG Lei,MA Zihua,CHEN Yusi,YANG Ting,YANG Qin,XIE Rujia

• 1:贵州医科大学贵州省常见慢性疾病发病机制及药物研究重点实验室病理生理学教研室

摘要(Abstract)：

目的:探讨辛二酰苯胺异羟肟酸(SAHA)联合索拉菲尼(SOR)对人肝癌(HepG2)细胞增殖与凋亡的影响,并探讨其可能的分子机制。方法:采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法(MTT)法检测SAHA联合SOR对HepG2细胞增殖的抑制作用,流式细胞术检测SAHA联合SOR对HepG2细胞凋亡的影响,Western blot法检测SAHA联合SOR对HepG2细胞中葡萄糖调节蛋白78(GRP78)、蛋白激酶R样内质网激酶(PERK)、磷酸化PERK(p-PERK)及活化转录因子4(ATF4)蛋白表达的影响。结果:与单独的SAHA及SOR组比较,SAHA联合SOR可使HepG2细胞增殖率明显下降、并显著促进细胞凋亡,差异有统计学意义(P<001);Western blot检测发现,SAHA联合SOR可显著上调GRP78、p-PERK及ATF4的表达水平,差异有统计学意义(P<005)。结论:SAHA联合SOR可显著增强对HepG2细胞增殖的抑制作用、并促进肝癌细胞凋亡,其机制可能与激活内质网应激凋亡信号通路有关。
Objective: To investigate the effect of similamide isohydroxyxamic acid( SAHA combined with Sorafini(SOR) on proliferation and apoptosis of human liver cancer(HepG2) cells and its possible molecular mechanism.Methods: The Inhibitory effect of SAHA combined with SOR on proliferation of HepG2 cells was examined by 3-(4,5-dimethylthiazole-2)-2 and 5-diphenyltetrazol bromide(MTT). Effect of SAHA combined with SOR on apoptosis of HepG2 cell was examined by flow cytometry. The effects of SAHA combined with SOR on the expression of glucose regulatory protein 78(GRP78), protein kinase R-like endoplasmic reticulum kinase(PERK), phosphorylated PERK(p-PERK) and activated transcription factor 4(ATF4) protein in HepG2 cells were examined by the method of Western blot.Results: Compared with SAHA and SOR group alone, SAHA combined with SOR could significantly decrease the proliferation rate of HepG2 and promote apoptosis, and the difference was statistically significant(P< 0. 01). Western blot showed that SAHA combined with SOR significantly upregulated the expression levels of GRP78, p-PERK and ATF4, and the difference was statistically significant(P< 0. 05).Conclusion: SAHA combined with SOR can significantly enhance the inhibition of HepG2 cell proliferation and promote the apoptosis of hepatoma cells, and its mechanism may be related to the activation of endoplasmic reticulum stress apoptosis signaling pathway.

关键词(KeyWords)： 肝肿瘤;内质网;细胞凋亡;细胞增殖;索拉菲尼;辛二酰苯胺异羟肟酸
liver neoplasms;endoplasmic reticulum;apoptosis;cell proliferation;sorafenib(SOR);suberoylanilide hydroxamic acid(SAHA)

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目（81560105）;; 贵州医科大学2018年度学术新苗培养及创新探索专项项目培育项目[黔科合平台人(2018)5779-19]

作者(Author): 蔡爽,韩冰,郑璐,汤雷,马子华,陈雨丝,杨婷,杨勤,谢汝佳
CAI Shuang,HAN Bing,ZHENG Lu,TANG Lei,MA Zihua,CHEN Yusi,YANG Ting,YANG Qin,XIE Rujia

DOI: 10.19367/j.cnki.1000-2707.2020.02.005

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