Cyanidin-3-O-glucoside inhibits the β-catenin/MGMT pathway by upregulating miR-214-5p to reverse chemotherapy resistance in glioma cells

Abstract

Overcoming resistance to alkylating agents has important clinical significance in glioma. Cyanidin-3-O-glucoside (C3G) has a tumor-suppressive effect on tumor cells. However, whether it plays a role in temozolomide resistance in glioma is still unclear. We constructed a TMZ-resistant LN-18/TR glioma cell line, observed the effect of C3G on TMZ resistance in this cell line, and explored the role of miR-214-5p in chemoresistance. Results showed that β-catenin and MGMT were significantly upregulated in LN-18/TR cells. C3G upregulated miR-214-5p and enhanced the cytotoxic effect of temozolomide on LN-18/TR cells. Contrarily, C3G downregulated β-catenin and MGMT. Moreover, the miR-214-5p mimic downregulated β-catenin and MGMT in LN-18/TR cells, whereas the miR-214-5p inhibitor had the opposite effect; the miR-214-5p inhibitor significantly blocked the C3G-induced downregulation of β-catenin and MGMT. C3G or the miR-214-5p mimic enhanced temozolomide-induced apoptosis in LN-18/TR cells, whereas the miR-214-5p inhibitor blocked this effect. Furthermore, C3G or miR-214-5p agomir combined with TMZ significantly inhibited the growth of LN-18/TR tumors. Collectively, our research discovered the potential signaling mechanism associated with C3G-mediated suppression of TMZ resistance in LN-18/TR cells through miR-214-5p, which can facilitate the treatment of MGMT-induced resistance in glioma cells.