丙戊酸对食管癌细胞增殖凋亡的影响及其抗肿瘤活性机制的研究

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摘要目的探索丙戊酸（VPA）对食管癌细胞增殖凋亡的影响以及Bcl-2 蛋白、Caspase 蛋白表达及信号转导通路的分子机制。方法将食管癌ECa-109 细胞株培养于PRMI1640 培养液，按照溶剂对照和溶度梯度分组：空白对照及VPA 0.25 mmol/L、0.5 mmol/L、1.0 mmol/L、2.0 mmol/L、4.0 mmol/L。根据不同的药物浓度处理细胞24、48、72 h后，观察食管癌ECa-109 细胞的变化，运用不同的检测方法检测食管癌ECa-109 细胞的细胞活力、细胞凋亡及周期的变化；Western Blot 检测CyclinD1、p21、Survivin、Bcl-2 和Caspase 蛋白及PI3K/Akt 和MAPK 信号转导通路的变化。结果 VPA 可有效影响ECa-109 细胞的活力、增殖和分化，能够通过诱导细胞周期阻滞使细胞产生凋亡。Western Blot 实验结果显示，VPA 可以影响ECa-109 细胞中Bcl-2、Survivin 以及Caspase 蛋白的表达；VPA 可明显降低ECa-109 细胞中CyclinD1 蛋白表达水平，同时增加p21 蛋白的表达，使其能够影响信号通路PI3K/Akt 和MAPK 途径中AKT、MAPK 等关键蛋白的磷酸化。结论 VPA 能够影响食管癌细胞的增殖凋亡，并具有浓度依赖性；能够通过影响多种蛋白激酶途径中的信号通路、生存蛋白的表达以及PI3K/Akt 和MAPK 信号通路的表达而影响食管癌细胞的生长。

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	杨鲸蓉
	柳亚明
	张锦灿
	曾志勇

关键词 ：组蛋白去乙酰化酶, 组蛋白去乙酰化酶抑制剂, 食管癌, ECa-109 细胞, 丙戊酸, Bcl-2, Caspase3, Akt

Abstract：Objective To explore the effect of Valproic Acid (VPA) on proliferation and apoptosis of esophageal cancer cells,and expression of Bcl-2,Caspase protein,as well as molecular mechanisms of signal transduction pathways. Methods ECa-109 cell line of esophageal cancer was cultured with PRMI1640 medium, and grouped according to solvent control and solubility gradient：blank control and VPA 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, 2.0 mmol/L, 4.0 mmol/L.After treating cells for 24, 48 and 72 hours according to different drug concentrations, the changes of esophageal cancer ECa-109 cells were observed, and different detection methods were used to detect the changes of cell viability, apoptosis and cycle of esophageal cancer ECa-109 cells.Western Blot was used to detect CyclinD1, p21, Survivin, Bcl-2,Caspase protein and PI3K/Akt and MAPK signal transduction pathway changes. Results VPA showed different extent changes on vitality, proliferation, differentiation of ECa-109 cells, could induce cell apoptosis by inducing cell cycle arrest.Western Blot experiment results showed that VPA could affect the expression of Bcl-2, Survivin and Caspase proteins in ECa-109 cells.VPA could significantly reduce the expression level of CyclinD1 protein in ECa-109 cells and increase the expression of p21 protein, which influenced the phosphorylation of key proteins such as AKT and MAPK in the signaling pathway PI3K/Akt and MAPK pathway. Conclusion VPA has an effect on the proliferation and apoptosis of esophageal cancer cells and it is concentration-dependent, which can affect the growth of esophageal cancer cells through the signaling pathways of multiple protein kinase pathways, the expression of survival proteins, the expression of PI3K/Akt and MAPK signaling pathways.

Key words： Histone deacetylase Histone deacetylase inhibitors Esophageal cancer ECa-109 cells Valproic Acid Bcl-2 Caspase3 Akt

基金资助:福建省自然科学基金项目（2017J01223）

引用本文:

杨鲸蓉; 柳亚明; 张锦灿; 曾志勇. 丙戊酸对食管癌细胞增殖凋亡的影响及其抗肿瘤活性机制的研究[J]. 中国当代医药, 2020, 27(15): 4-9.
YANG Jing-rong; LIU Ya-ming; ZHANG Jin-can; ZENG Zhi-yong. Effect of Valproic Acid on proliferation and apoptosis of esophageal cancer cells and study on its antitumor activity mechanism. 中国当代医药, 2020, 27(15): 4-9.

链接本文:

http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2020/V27/I15/4

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