Synergistic therapeutic effect and mechanism of Cryptotanshinone combined with Matrine on ovarian cancer.

Abstract

Chemotherapy resistance in ovarian cancer (OC) poses a significant challenge in clinical treatment. 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. Cell proliferation was assessed via the CCK-8 assay; apoptosis was analysed 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. 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. 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. Cryptotanshinone and matrine exert anti-OC effects through multiple mechanisms by inhibiting the PI3K/Akt/mTOR pathway, effectively reversing drug resistance.