Baohuoside I inhibits resistance to cisplatin in ovarian cancer cells by suppressing autophagy via downregulating HIF‐1α/ATG5 axis

Abstract

AbstractSince chemotherapy's therapeutic impact is diminished by drug resistance, treating ovarian cancer is notably challenging. Thereafter, it is critical to develop cutting‐edge approaches to treating ovarian cancer. Baohuoside I (derived from Herba Epimedii) is reported to have antitumor properties in various malignancies. It is unknown, however, what role Baohuoside I plays in cisplatin (DDP)‐resistant ovarian cancer cells. 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐phenytetrazoliumromide (MTT), colony formation, and flow cytometry assay were used to investigate the impact of Baohuoside I on ovarian cancer A2780 cells and DDP‐resistant A2780 (A2780/DDP) cells. The level of microtubule associated protein 1 light chain 3 (LC3) was determined using immunofluorescence staining. Utilizing the mRFP‐GFP‐LC3B tandem fluorescent probe allowed us to analyse the autophagy flux. Analysis of mRNA and protein level was performed using RT‐qPCR and Western blot analysis, respectively. The interaction between hypoxia inducible factor 1 subunit alpha (HIF‐1α) and autophagy related 5 (ATG5) promoter was investigated by dual luciferase and ChIP assay. Additionally, evaluation of Baohuoside I's role in ovarian cancer was performed using a nude mouse xenograft model. Baohuoside I decreased the viability and proliferation and triggered the apoptosis of both A2780 and A2780/DDP cells in a concentration‐dependent manner. Baohuoside I also increased the sensitivity of A2780/DDP cells to DDP. Concurrently, HIF‐1α could promote A2780/DDP cells resistance to DDP. In addition, HIF‐1α could induce the autophagy of A2780/DDP cells through transcriptionally activating ATG5, and Baohuoside I imporved the chemosensitivity of A2780/DDP cells to DDP by downregulating HIF‐1α. Moreover, Baohuoside I could inhibit the chemoresistance to DDP in ovarian cancer in vivo. Baohuoside I sensitizes ovarian cancer cells to DDP by suppressing autophagy via downregulating the HIF‐1α/ATG5 axis. Consequently, Baohuoside I might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of drug treatment for ovarian cancer.