RGFP966通过PI3K/AKT通路抑制胃癌细胞增殖
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1.盐城市第二人民医院肿瘤内科;2.扬州大学附属苏北人民医院肿瘤科

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江苏省自然科学基金面上项目(编号:BK20211115)* 通信作者(Corresponding author):张先稳,E-mail: zhangxwwok@163.com


RGFP966 inhibits the proliferation of gastric cancer cells through PI3K/AKT pathway
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1.Department of Oncology, Yancheng Second People'2.'3.s Hospital;4.Department of Oncology, Subei People'5.s Hospital Affiliated to Yangzhou University

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Natural Science Foundation of Jiangsu Province (BK20211115)

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    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细胞系后各组细胞的活力;细胞克隆形成实验检测RGFP966对胃癌细胞形成细胞集落能力的影响;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、CyclinA2、CyclinD1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可显著的抑制胃癌细胞MKN-45和MGC-803的增殖能力、细胞集落形成能力。与对照组相比,流式细胞术显示RGFP966诱导胃癌细胞在G0/G1期阻滞。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、CyclinA2、CyclinD1表达均下降,进一步结果显示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在G0/G1期阻滞,其作用机制可能与RGFP966抑制PI3K/AKT信号通路有关。

    Abstract:

    Objective: To investigate the effects of histone deacetylase 3 inhibitor RGFP966 on proliferation and cell cycle of gastric cancer cells and its mechanism. Methods: The activity of MN-45 and MGC-803 cell lines treated with RGFP966 was detected by CCK-8 method.The effect of RGFP966 on the cytoclonal ability of gastric cancer cells was detected by cell cloning assay.Cell cycle was detected by flow cytometry.The expressions of Ki-67, c-Myc, CyclinA2, CyclinD1 and PI3K/AKT signaling pathway were detected by Westernblot assay. Results: Compared with the control group, RGFP966 could significantly inhibit the proliferation and cloning ability of MSN-45 and MGC-803 gastric cancer cells.Compared with the control group, flow cytometry showed that RGFP966 blocked the cell cycle in the G0/G1 phase.Compared with the control group, proliferation-related proteins Ki-67 and c-Myc were decreased after treatment with RGFP966, and the expressions of CyclinA2 and CyclinD1 were decreased. Further results showed that RGFP966 could significantly reduce the phosphorylation levels of PI3K and AKT. Conclusion: RGFP966 inhibits the proliferation of gastric cancer cells and blocks the cycle in G0/G1 phase, which may be related to the inhibition of PI3K/AKT signaling pathway by RGFP966.

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  • 收稿日期:2023-05-15
  • 最后修改日期:2023-07-09
  • 录用日期:2023-10-25
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