Ginsenoside Rg2 inhibit the cell viability of cisplatin-resistant epithelial ovarian cancer by suppressing CACNA1G-mediated calcium signaling.

Authors

Han Chen, Jiayi Wan, Siwen Lv, Chuanxiang Yao, Ye Tong, Xiutian Peng, Huiwen Wang, Siyuan Hou, Biqing Wu, Yinping Jin, Jiazhe Song, Kai Xue

Published in

Toxicology and applied pharmacology. Pages 118031. Sep 11, 2026. Epub Sep 11, 2026.

Abstract

Most patients with epithelial ovarian cancer (EOC) treated with cisplatin (cDDP) ultimately develop resistance. Owing to its anti-tumor effects and low toxicity, ginsenoside Rg2 (G-Rg2) is regarded as a potential active compound for the chemotherapy of EOC. By leveraging expression profiles of cDDP-sensitive and -resistant EOC patients from GEO datasets, we employed weighted gene co-expression network analysis (WGCNA) to screen for candidate differentially expressed genes relevant to the treatment of cDDP-resistant EOC. Based on this analysis, we identified the key target of G-Rg2 for addressing cDDP resistance in EOC through network pharmacology, clinical data analysis, and molecular docking techniques. Following screening, CACNA1G was selected as the potential target of G-Rg2 for treating cDDP-resistant EOC. Subsequently, G-Rg2 was extracted from American ginseng berry using a chromatographic separation and purification method involving a saturated n-butanol layer. Experimental validation was performed via RNA sequencing, immunostaining western blot, and flow cytometry in cDDP-resistant EOC cells to ascertain the alterations induced by G-Rg2 treatment. The stereoisomers of G-Rg2 [20(S)-G-Rg2 and 20(R)-G-Rg2] were utilized to treat cDDP-resistant EOC cells, demonstrating that G-Rg2 inhibits CACNA1G-mediated calcium signaling and downstream ERK phosphorylation, processes associated with cell proliferation. Compared to 20(S)-G-Rg2, 20(R)-G-Rg2 exhibited a more significant inhibitory effect on the CACNA1G-mediated calcium influx and downstream signaling, avoiding activation of anti-apoptotic pathways. Collectively, this study elucidates that G-Rg2 inhibits the cell viability of cDDP-resistant EOC by suppressing CACNA1G-mediated calcium signaling pathway, suggesting its potential application as an adjuvant chemotherapy agent for cDDP-resistant EOC.

PMID:
42727823
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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