首页|期刊导航|海南医学院学报|欣胃颗粒调控METTL6/CyclinD1通路对胃癌细胞增殖、凋亡和细胞周期的影响

欣胃颗粒调控METTL6/CyclinD1通路对胃癌细胞增殖、凋亡和细胞周期的影响OA北大核心CSTPCD

Effects of Xinwei granules on the METTL16/CyclinD1 pathway in gastric cancer cell proliferation,apoptosis,and cell cycle

中文摘要英文摘要

目的:观察欣胃颗粒对胃癌细胞METTL16/CyclinD1通路和增殖、凋亡和细胞周期的影响,阐明其治疗胃癌的分子机制.方法:采用CCK8法检测不同浓度欣胃颗粒对胃癌细胞株(MKN-45)细胞活性的影响,采用流式细胞术检测细胞凋亡和细胞周期的分布,采用 Western blot和 RT-qPCR法检测METTL16/CyclinD1通路中相关分子的表达,采用斑点杂交检测CyclinD1的m6A甲基化修饰水平.结果:与空白组相比,欣胃颗粒能够显著促进MKN-45细胞凋亡水平,增加G0/G1 期比例,降低S期比例,下调CyclinD1、CDK4、E2F1和METTL16蛋白的表达和p-Rb/Rb的比值,差异均具有统计学意义(P<0.01).此外,欣胃颗粒能够显著下调METTL16和CyclinD1 mRNA的表达,抑制CyclinD1的m6A甲基化修饰水平,差异均具有统计学意义(P<0.01).结论:欣胃颗粒通过抑制METTL16介导的CyclinD1的m6A甲基化修饰水平,从而发挥阻断G1期向S期转化、抑制细胞增殖和促进细胞凋亡的作用.

Objective:To investigate the effects of Xinwei granules on the METTL16/CyclinD1 pathway and proliferation,apoptosis,and cell cycle of gastric cancer cells,and to elucidate the molecular mechanisms underlying its therapeutic potential in gastric cancer.Methods:Cell viability of the MKN-45 gastric cancer cell line was assessed using the CCK-8 assay following treat-ment with various concentrations of gastric-derived granules.Flow cytometry was employed to analyze apoptosis and cell cycle dis-tribution.Western blot and RT-qPCR analyses were used to measure the expression of key molecules in the METTL16/CyclinD1 pathway.Spot hybridization was performed to detect m6A methylation modifications of CyclinD1.Results:Compared to the con-trol group,gastric-derived granules significantly increased apoptosis in MKN-45 cells,elevated the proportion of cells in the G1 phase,reduced the proportion in the S phase,and downregulated the expression of CyclinD1,CDK4,E2F1,and METTL16 proteins as well as the p-Rb/Rb ratio(P<0.01).Additionally,gastric-derived granules significantly decreased the mRNA expres-sion levels of METTL16 and CyclinD1,and inhibited CyclinD1 m6A methylation modifications(P<0.01).Conclusion:Xinwei granules exert their effects by inhibiting METTL16-mediated m6A methylation of CyclinD1,thereby blocking the transition from the G1 phase to the S phase,suppressing cell proliferation,and promoting apoptosis.

吴丽丽;张冉;刘馨瑶;张杨;王静滨

广州中医药大学深圳医院(福田),广东 深圳 518034黑龙江中医药大学附属第一医院,黑龙江 哈尔滨 150040

中医学

欣胃颗粒METTL16/CyclinD1信号通路m6A甲基化修饰胃癌前病变

Xinwei granulesMETTL16/CyclinD1 signaling pathwaym6A methylation modificationsPrecancerous le-sions of gastric cancer

《海南医学院学报》 2024 (024)

1869-1875 / 7

This study was supported by the National Natural Science Foundation of China(81973601);Shenzhen Futian District Health System Research Project(FTWS2022033 and FTWS2023099);Funding Support for the Construction of Clinical Key Specialties in Futian District,Shenzhen. 国家自然科学基金资助项目(81973601);深圳市福田区卫生健康系统科研项目(FTWS2022033);深圳市福田区卫生健康系统科研项目(FTWS2023099);深圳市福田区临床重点专科建设经费资助

10.13210/j.cnki.jhmu.20241022.001

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