Abstract

Background Chemotherapy resistance in ovarian cancer (OC) poses a significant challenge in clinical treatment, with cisplatin resistance limiting therapeutic efficacy. We aim to explore the inhibitory impact of the synergistic action of Cryptotanshinone and Matrine on OC cells, along with its molecular mechanism, thereby providing a novel therapeutic strategy for OC management.Methods Cell proliferation was assessed via the CCK-8 assay; apoptosis was analyzed by flow cytometry; cell migration and invasion were evaluated using the Transwell assay; gene expression was measured with qRT-PCR. A nude mouse xenograft model was established to verify in vivo efficacy. The role of the PI3K/Akt/mTOR pathway was elucidated through rescue experiments.Results Cyptotanshinone and Matrine inhibited OC cell proliferation in a dose- and time-dependent manner. Combination therapy synergistically enhanced the antiproliferative effects, inducing apoptosis, suppressing migration and invasion, and downregulating the expression of MMP2 and MMP9. In cisplatin-resistant cells, the combination reversed drug resistance and reduced P-gp expression. In vivo, the combination significantly suppressed tumor growth and modulated the expression of molecular markers (e.g., Ki-67, Bax, Bcl-2, and Caspase-3), with no notable toxicity observed in the liver or kidneys. Mechanistically, the combination markedly downregulated transcription of key genes in the PI3K/Akt/mTOR pathway. Rescue experiments confirmed that pathway inhibition underpins the synergistic effect.Conclusions Cryptotanshinone and Matrine exert anti-OC effects through multiple mechanisms by inhibiting the PI3K/Akt/mTOR pathway, effectively reversing drug resistance. This study provides experimental evidence and potential therapeutic strategies for OC treatment and offers prospects for optimizing clinical drug regimens.