RGFP966通过PI3K/AKT通路抑制胃癌细胞增殖  

RGFP966 inhibits the proliferation of gastric cancer cells through PI3K/AKT pathway

作　　者：董正宇 张先稳[3] 张林 DONG Zhengyu;ZHANG Xianwen;ZHANG Lin(Medical College of Yangzhou University,Yangzhou 225001;Department of Oncology,Yancheng Second People’s Hospital,Yancheng 224003;Department of Oncology,North Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China)

机构地区：[1]扬州大学医学院,江苏扬州225001 [2]盐城市第二人民医院肿瘤内科,江苏盐城224003 [3]扬州大学附属苏北人民医院肿瘤科,江苏扬州225001

出　　处：《南京医科大学学报（自然科学版）》2023年第11期1503-1508,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省自然科学基金(BK20211115)。

摘　　要：目的:探讨组蛋白去乙酰化酶3特异性抑制剂RGFP966对胃癌细胞增殖能力和细胞周期的影响及其作用机制。方法:采用CCK-8法检测RGFP966处理MKN-45和MGC-803细胞后各组细胞的活力;细胞克隆形成实验检测RGFP966对胃癌细胞集落形成能力的影响;流式细胞术检测细胞周期;Western blot实验检测细胞增殖和周期相关蛋白Ki-67、c-Myc、Cyclin A2、Cyclin D1以及PI3K/AKT信号通路相关蛋白的表达情况。结果:与对照组相比,RGFP966可显著抑制胃癌细胞MKN-45和MGC-803的增殖能力、集落形成能力。与对照组相比,流式细胞术显示RGFP966诱导胃癌细胞阻滞在G0/G1期。与对照组相比,RGFP966处理后细胞增殖和周期相关蛋白Ki-67、c-Myc、Cyclin A2、Cyclin D1表达均下降,RGFP966可显著降低PI3K和AKT的磷酸化水平。结论:RGFP966抑制胃癌细胞的增殖能力并诱导胃癌细胞阻滞在G0/G1期,其作用机制可能与RGFP966抑制PI3K/AKT信号通路有关。Objective:The objective of the current study was to investigate the effects of RGFP966,a histone deacetylase 3 inhibitor,on the proliferation and cell cycle of gastric cancer cells,as well as its underlying mechanism.Methods:The activity of MKN-45 and MGC-803 cell lines treated with RGFP966 was assessed using the CCK-8 method.The cytoclonal ability of gastric cancer cells in response to RGFP966 was examined using a cell cloning assay.Flow cytometry was employed to analyze the cell cycle distribution.The protein expressions of Ki-67,c-Myc,Cyclin A2,Cyclin D1,and the PI3K/AKT signaling pathway were evaluated through Western blot analysis.Results:Compared with the control group,RGFP966 significantly inhibited the proliferation and clonal ability of MKN-45 and MGC-803 gastric cancer cells.Flow cytometry analysis revealed that RGFP966 induced cell cycle arrest at the G0/G1 phase.Furthermore,treatment with RGFP966 resulted in reduced levels of the proliferation-related proteins Ki-67 and c-Myc,as well as decreased expressions of Cyclin A2 and Cyclin D1.Moreover,RGFP966 significantly suppressed the phosphorylation levels of PI3K and AKT.Conclusion:Our findings indicate that RGFP966 inhibits the proliferation of gastric cancer cells and induces cell cycle arrest at the G0/G1 phase.These effects may be attributed to the inhibition of the PI3K/AKT signaling pathway by RGFP966.

关 键 词：RGFP966 胃癌细胞 增殖 PI3K/AKT 

分 类 号：R735.2[医药卫生—肿瘤]