TRPC广谱抑制剂SKF96365协同顺铂对人胃癌HGC-27细胞的作用及相关机制的研究

doi:10.13418/j.issn.1001-165x.2025.4.11

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中国临床解剖学杂志 ›› 2025, Vol. 43 ›› Issue (4) : 426-435. DOI: 10.13418/j.issn.1001-165x.2025.4.11

实验研究

TRPC广谱抑制剂SKF96365协同顺铂对人胃癌HGC-27细胞的作用及相关机制的研究

冯娜，董升，史丹丹，黄晓敏，亢鹏举，李文春，贺细菊*

作者信息 +

Effects of TRPC broad-spectrum inhibitor SKF96365 combined with cisplatin on human gastric cancer HGC-27 cells and related mechanisms

Feng Na, Dong Sheng, Shi Dandan, Huang Xiaomin, Kang Pengju, Li Wenchun, He Xiju*

Author information +

文章历史 +

摘要

目的探讨SKF96365联合顺铂对HGC-27细胞抑制作用及其分子机制的研究。方法采用2.5、5、7.5、10 μmol/L SKF96365与顺铂联合作用HGC-27细胞；CCK-8、划痕实验检测细胞活力和迁移；JC-1、MitoROS、Rhod-2/AM荧光探针检测细胞线粒体膜电位、活性氧及钙离子浓度的变化；Hoechst染色和流式细胞术检测细胞凋亡情况；Western blot检测细胞凋亡、自噬蛋白及PI3K/AKT/BAD信号通路相关蛋白的表达。结果与对照组相比，联合用药组能够显著抑制HGC-27细胞的增殖与迁移，诱导细胞线粒体功能受损，促使细胞凋亡率增加（P<0.05）。Western blot结果显示联合用药可促进胃癌细胞凋亡、自噬相关蛋白的表达，且显著抑制了细胞中PI3K/AKT/BAD信号通路磷酸化水平。结论 SKF96365联合顺铂通过抑制PI3K/AKT/BAD通路的磷酸化水平诱导胃癌细胞启动线粒体凋亡途径和细胞自噬，促进细胞凋亡。

Abstract

Objective To explore SKF96365 combined with cisplatin on human gastric cancer HGC-27 cells and its molecular mechanism. Methods HGC-27 cells were treated with 2.5, 5, 7.5, 10 μmol/L SKF96365 combined with cisplatin. CCK-8 and scratch healing assay were used to detect cell viability and migration. JC-1, MitoROS, Rhod-2/AM fluorescent probes were used to detect the changes of mitochondrial membrane potential, reactive oxygen species and Ca2+ concentration. Hoechst staining and flow cytometry were used to detect cell apoptosis. The expressions of apoptosis, autophagy protein and PI3K/AKT/BAD signaling pathway were detected by Western blot. Results Compared with the control group, the combined treatment group could significantly inhibit the proliferation and migration of HGC-27 cells, induce cell mitochondrial dysfunction, and promote the increase of cell apoptosis rate (P<0.05). Western blot results showed that the combined treatment could promote apoptosis and the autophagy related proteins expression in gastric cancer cells, and significantly inhibit the phosphorylation of PI3K/AKT/BAD signaling pathway in cells. Conclusions SKF96365 combined with cisplatin induces gastric cancer cells to initiate mitochondrial apoptosis pathway and protective autophagy by inhibiting the phosphorylation level of PI3K/Akt/Bad pathway.

导出引用

冯娜, 董升, 史丹丹, 黄晓敏, 亢鹏举, 李文春, 贺细菊. TRPC广谱抑制剂SKF96365协同顺铂对人胃癌HGC-27细胞的作用及相关机制的研究[J]. 中国临床解剖学杂志. 2025, 43(4): 426-435 https://doi.org/10.13418/j.issn.1001-165x.2025.4.11

Feng Na, Dong Sheng, Shi Dandan, Huang Xiaomin, Kang Pengju, Li Wenchun, He Xiju. Effects of TRPC broad-spectrum inhibitor SKF96365 combined with cisplatin on human gastric cancer HGC-27 cells and related mechanisms[J]. Chinese Journal of Clinical Anatomy. 2025, 43(4): 426-435 https://doi.org/10.13418/j.issn.1001-165x.2025.4.11

中图分类号： R73

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