Astragalus polysaccharides sensitize ovarian cancer stem cells to PARPi by inhibiting mitophagy via PINK1/Parkin signaling.

ABSTRACT: Ovarian cancer (OC) remains the most lethal gynecological malignant tumor. PARP inhibitors (PARPi) have significantly improved survival, particularly in patients with OC with BRCA1/2 mutations. However, the majority of patients eventually develop resistance to PARPi. Cancer stem cells (CSCs) are considered the source of drug resistance in cancer. Our study found that the synergistic effect of astragalus polysaccharides (APSs) and PARPi was observed in ovarian cancer stem cells (OCSCs) by decreasing cell viability and self-renewal potential while inducing apoptosis. The present study also demonstrated that OCSCs had increased mitophagy. Furthermore, it was observed that APS in combination with PARPi inhibits mitophagy and downregulates the PINK1 protein level in OCSCs. The overexpression of

SUBMITTER: Peng Q 

PROVIDER: S-EPMC11301338 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature