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

• Published in: Molecular carcinogenesis 2023-10, Vol.62 (10), p.1474-1486
• Main Authors: Zhou, Yun, Liu, Tongyu, Wu, Qiaoling, Wang, Huihui, Sun, Yang
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Cell proliferation; Chemoresistance; Chemotherapy; Cisplatin; Drug resistance; Flow cytometry; Fluorescent indicators; Hypoxia; Immunofluorescence; Malignancy; Ovarian cancer
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.23590

Since 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.