半夏泻心汤对胃癌细胞凋亡的作用机制研究OACHSSCD
Mechanisms of Banxia Xiexin Decoction on Apoptosis of Gastric Cancer Cells
目的:研究半夏泻心汤对胃癌细胞MKN-45 N6-甲基腺嘌呤(m6A)甲基化的影响,以及进一步促进胃癌细胞凋亡的作用机制.方法:30只大鼠按照随机数字表法分为空白血清组、西药组及半夏泻心汤组,每组10只,分别给予半夏泻心汤组灌胃、生理盐水灌胃、5-氟尿嘧啶(5-FU)尾静脉注射,连续给药2周,末次给药后行腹主动脉取血,制备含药血清.采用比色法检测各组细胞N6-甲基腺嘌呤(m6A)核糖核酸(RNA)甲基化水平,实时荧光定量聚合酶链反应(RT-PCR)检测各组细胞甲基转移酶3(METTL3)、凋亡调节因子Bcl相关X蛋白(Bax)、B细胞淋巴瘤-2基因(Bcl-2)、胱天蛋白酶-3(Caspase-3)mRNA的表达;采用蛋白质印迹法检测各组细胞METTL3、Bax、Bcl-2、Caspase-3蛋白的表达.结果:与空白组比较,半夏泻心汤组MKN-45胃癌细胞METTL3表达水平及m6A RNA甲基化水平明显下降,Bcl-2信使核糖核酸(mRNA)水平及蛋白表达水平明显下降,Bax、Caspase-3及蛋白水平明显升高,差异有统计学意义(P<0.05).结论:半夏泻心汤能够通过下调METTL3介导的m6A甲基化水平,从而上调促凋亡相关蛋白Bax、Caspase-3的表达,降低抗凋亡因子Bcl-2的表达,达到抗肿瘤的目的.
Objective:To investigate the effects of Banxia Xiexin Decoction on N6-methyladenosine(m6A)methylation in MKN-45 gastric cancer cells and its mechanisms in promoting apoptosis.Methods:Thirty rats were randomly divided into three groups(n=10 each)according to the random number table method:blank serum group,western medicine group,and Banxia Xiexin Decoction group.Rats were treated for 2 weeks with intragastric administration of Banxia Xiexin Decoction,intragastric administration of nor-mal saline,or tail vein injection of 5-fluorouracil(5-FU),respectively.After the final administration,blood was collected from the abdominal aorta to prepare drug-containing serum.The m6A RNA methylation level in MKN-45 cells was measured by colorimetric assay.RT-PCR was used to detect mRNA expression of methyltransferase-like 3(METTL3),B-cell lymphoma-2(Bcl-2)-associated X protein(Bax),Bcl-2,and Caspase-3.Protein expression of METTL3,Bax,Bcl-2,and Caspase-3 was assessed by Western blot.Results:Compared with the blank serum group,Banxia Xiexin Decoction significantly decreased METTL3 expression and m6A RNA methylation levels in MKN-45 cells,reduced Bcl-2 mRNA and protein expression,and increased Bax and Caspase-3 mRNA and protein expression(P<0.05).Conclusion:Banxia Xiexin Decoction may exert anti-tumor effects by downregulating METTL3-mediated m6A methylation,thereby upregulating pro-apoptotic proteins Bax and Caspase-3 and downregulating the anti-apoptotic protein Bcl-2.
顾文;周春祥;黄华建
上海市浦东新区肺科医院中医科,上海,200120南京中医药大学,南京,210023杭州市临安区中医院外三科,311300
医药卫生
胃癌甲基转移酶3N6-甲基腺嘌呤凋亡相关因子胱天蛋白酶-3作用机制
Gastric cancerMethyltransferase-like 3(METTL3)N6-methyladenosineApoptosis-related factorsCaspase-3Mech-anism
《世界中医药》 2026 (5)
795-799,808,6
国家自然科学基金面上项目(82074504)浦东新区中医药传承创新发展示范点项目(YC-2023-0402).
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