甘草酸通过抑制OGT-MDH1信号通路减轻三阴性乳腺癌对紫杉醇的耐药性

doi:10.3969/j.issn.1004-616x.2025.01.006

Abstract

Abstract: OBJECTIVE： Paclitaxel resistance (PR) is a significant reason for chemotherapy failure in triple-negative breast cancer (TNBC). This study investigated the sensitizing effect of glycyrrhetinic acid (GA) on paclitaxel (PTX) resistant cells in TNBC and its mechanism of action. METHODS： PTX-resistant TNBC cell lines，MDA-MB-231 and BT-20， were used. Cells were divided into PTX treatment groups and low，medium，and high-dose GA combined groups (PTX treatment plus 2.5，5 or 10 μmol/L GA). Cell viability was assessed using the Sulforhodamine B colorimetric assay. In addition，cells were divided into DMSO control group，40 nmol/L PTX treatment group，10 μmol/L GA treatment group，and 40 nmol/L PTX and 10 μmol/L GA combined group. Colony formation assay was performed to detect cell proliferation，and flow cytometry was used to detect cell apoptosis. Western blot experiments were conducted to measure the protein levels of Bcl-2，Bax，c-PARP，OGT，and MDH1. RESULTS： MDA-MB-231 were treated with 2.5，5 and 10 μmol/L GA combined with PTX for 5 days. The results of sulforhodamine B colorimetric assay showed that compared with the PTX group，the combined treatment led to a decrease in the viability of the cells in a dose-dependent manner. The results of cell colony formation assay showed that compared with the control group，the colony formation rate of cells in the combined treatment group was reduced. Flow cytometry results showed that compared with the PTX group，the proportion of subG₁ group cells increased after the combined treatment for 48 and 72 h. Western blot experiments showed that the expression level of Bcl-2 protein in the combined treatment group was reduced，and the expression levels of Bax and c-PARP proteins were increased. Western blot results showed that the combined treatment significantly inhibited O-GlcNAcylation glycosylation modification，and OGT and MDH1 protein expression levels. CONCLUSION： Glycyrrhetinic acid significantly enhanced the sensitivity of TNBC PTX-resistant cells to paclitaxel by inhibiting the OGT-MDH1 signaling pathway.

Key words: glycyrrhizic acid, OGT-MDH1 signaling pathway, triple-negative breast cancer, paclitaxel, drug resistance

CLC Number:

YU Pingyang, LI Jinyang, DOU He, XIAO Min. Glycyrrhizic acid reduces paclitaxel resistance in triple-negative breast cancer by inhibiting the OGT-MDH1 signaling pathway[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 33-38.

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Glycyrrhizic acid reduces paclitaxel resistance in triple-negative breast cancer by inhibiting the OGT-MDH1 signaling pathway

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