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

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

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Chinese Journal of Clinical Anatomy ›› 2025, Vol. 43 ›› Issue (4) : 426-435. DOI: 10.13418/j.issn.1001-165x.2025.4.11

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*

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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.

Key words

Gastric cancer; / / Transient receptor potential channel (TRPC); / / SKF96365; / / Cisplatin;Calcium overload; / / Apoptosis

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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

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