ScholarWorks@숙명여자대학교

초록

Despite therapeutic advances, ovarian cancer remains a major clinical challenge owing to its frequent metastasis and chemoresistance, which are often driven by cancer stem cells (CSCs) and proangiogenic signaling. Here we demonstrated that dihydroartemisinin (DHA), a derivative of the antimalarial drug artemisinin, inhibits CSC characteristics, tumor neovascularization and resistance to carboplatin via a microRNA-dependent mechanism in ovarian cancer. DHA substantially inhibited CSC properties, tumorigenicity and vascular endothelial growth factor A (VEGF-A)-mediated tumor neovascularization in ovarian cancer. Moreover, the combined treatment with DHA and carboplatin produced a synergistic effect that reduced tumor burden, chemoresistance and peritoneal dissemination in vivo. Mechanistically, DHA downregulated BMI-1 and VEGF-A/vascular endothelial growth factor receptor 2 (VEGFR2), which are critical factors in CSC maintenance and metastasis, via the upregulation of miR-200b. An analysis of ovarian tumor tissues collected from patients enrolled in our clinical cohort revealed that dual positivity for BMI-1 and VEGF-A was associated with poor progression-free survival. Overall, DHA targets the miR-200b-BMI-1/VEGF-A axis to suppress cancer stemness and metastatic potential, highlighting its therapeutic promise in overcoming the limitations of standard chemotherapy for ovarian cancer. The clinical trial number for this study is not applicable.

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