氯胍增强索托拉西布抑制KRAS<sup>G12C</sup>野生型膀胱癌细胞增殖和迁移的作用机制

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摘要 目的：探讨氯胍能否增强KRAS^G12C野生型膀胱癌细胞对索托拉西布的敏感性及其作用机制。方法：使用MTT、克隆形成实验以及Compusyn软件检测索托拉西布与氯胍联用能否增强对KRAS^G12C野生型膀胱癌细胞增殖的抑制作用以及联用效果如何。划痕实验检测其对细胞迁移能力的抑制作用,WB实验检测其对增殖相关蛋白的抑制作用。结果：索托拉西布与氯胍联用能够增强对KRAS^G12C野生型膀胱癌细胞增殖与迁移的抑制作用,并且对增殖相关蛋白p-cRAF以及p-ERK等的表达抑制作用增强。结论：氯胍通过抑制RAF/ERK通路增强KRAS^G12C野生型膀胱癌细胞对索托拉西布的敏感性。

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	张芝榕
	王伟帆
	肖迪
	杨小平

关键词 ：野生型膀胱癌细胞, KRAS^G12C, 氯胍, 索托拉西布, 增殖, 迁移, 作用机制

Abstract：Objective To explore whether proguanil can enhance the sensitivity of KRAS^G12C wild-type bladder cancer cells to sotorasib and its mechanism. Methods MTT, clone formation assay and Compusyn software were used to test whether the combination of sotorasib and proguanil can enhance the inhibition of KRAS^G12C wild-type bladder cancer cell proliferation and how the combined effect is. Scratch experiment was used to detect the inhibitory effect on cell migration, and finally, WB experiment was used to detect the inhibitory effect on proliferation related proteins. Results Sotorasib combined with proguanil enhanced the inhibition of proliferation and migration of KRAS^G12C wild-type bladder cancer cells. And the inhibitory effect on the expression of proliferation related proteins such as p-cRAF and p-ERK was enhanced. Conclusion Proguanil can enhance the sensitivity of KRAS^G12C wild-type bladder cancer cells to sotorasib by inhibiting RAF/ERK pathway.

Key words： wild-type bladder cancer cells KRAS^G12C proguanil sotorasib proliferation migration mechanism

收稿日期: 2023-10-28

中图分类号:	R363
	R96

基金资助:国家自然科学基金项目“ 双胍新衍生物SMK-002阻断PKM2入核下调脂质合成抑制EMT阻止膀胱癌转移的作用和机制研究”（82172653）

通讯作者: 杨小平,E-mail：xiaoping.yang@hunnu.edu.cn

作者简介: “#”:并列第一作者

引用本文:

张芝榕, 王伟帆, 肖迪, 杨小平. 氯胍增强索托拉西布抑制KRAS^G12C野生型膀胱癌细胞增殖和迁移的作用机制[J]. 湖南师范大学学报(医学版), 2023, 20(6): 9-13. ZHANG Zhirong, WANG Weifan, XIAO Di, YANG Xiaoping. Mechanism of Proguanil Enhancing the Inhibitory Effect of Sotorasib on Proliferation and Migration of KRAS^G12C Wild-type Bladder Cancer Cells. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(6): 9-13.

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http://yxb.hunnu.edu.cn/CN/ 或 http://yxb.hunnu.edu.cn/CN/Y2023/V20/I6/9

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