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

Abstract

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.

Baohuoside I chemosensitises breast cancer to paclitaxel by suppressing extracellular vesicle/CXCL1 signal released from apoptotic cells

“…This finding is consistent with the previous reports that BHS synergizes chemotherapy in multiple malignancies. For example, BHS inhibited cisplatin resistance in ovarian cancer by suppressing autophagy via downregulating the HIF‐1α/ATG5 axis (Zhou et al., 2023 ). BHS also potentiated paclitaxel chemotherapy in human melanoma by inducing apoptosis via inhibiting the TLR4 pathway (Wu et al., 2012 ).…”

“…Our previous study showed that BHS inhibits breast cancer growth and metastasis by suppressing TAM/CXCL1‐induced self‐renewal of CSCs (Wang et al., 2020 ). In addition to these direct cancer inhibition effects, recent studies revealed that BHS has the potential to act as an adjuvant agent to chemosensitise malignancies with other cytotoxic drugs (Wu et al., 2012 ; Zhou et al., 2023 ). For example, BHS synergistically interacted with cisplatin to chemosensitise ovarian cancer by suppressing autophagy via downregulating the HIF‐1α/ATG5 axis (Zhou et al., 2023 ).…”

“…In addition to these direct cancer inhibition effects, recent studies revealed that BHS has the potential to act as an adjuvant agent to chemosensitise malignancies with other cytotoxic drugs (Wu et al., 2012 ; Zhou et al., 2023 ). For example, BHS synergistically interacted with cisplatin to chemosensitise ovarian cancer by suppressing autophagy via downregulating the HIF‐1α/ATG5 axis (Zhou et al., 2023 ). BHS also potentiated paclitaxel‐induced apoptosis in human melanoma by inhibiting TLR4 signalling (Wu et al., 2012 ).…”

The emerging role of circular RNAs in cisplatin resistance in ovarian cancer: From molecular mechanism to future potential

“…Autophagy is a necessary cellular process for the physiological cellular turnover. Thereby, dysregulation in this process is one of the main cause of the tumorgenesis, progression of multiple malignancies and resistance to cisplatin treatment including ovarian cancer [ [198] , [199] , [200] ].…”

LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17

“…The risk factors for ovarian cancer include genetic and environmental factors, such as geographic differences and family history [ 2 , 3 ]. Chemotherapy is a commonly used therapeutic approach to ovarian cancer, but its efficiency is limited by drug resistance [ 4 ]. Early diagnosis is the most effective method to prevent advanced ovarian cancer [ 1 ].…”