Astragalus IV Undermines Multi-Drug Resistance and Glycolysis of MDA-MB-231/ADR Cell Line by Depressing hsa_circ_0001982-miR-206/miR-613 Axis
Hongchang Li, Zhihua Xia, Limin Liu, Gaofeng Pan, Junbin Ding, Jiazhe Liu, Jie Kang, Jindong Li, Daowen Jiang, Weiyan Liu
Abstract
Background: Allowing for the power of astragalus in improving cancer patients’ response to chemotherapy, we endeavored to clarify if hsa_circ_0001982-centered miRNA axes participated in the impact of astragaloside IV on multi-drug resistance (MDR) of triple-negative breast cancer (TNBC). Methods: TNBC patients were recruited into an Astragalus detoxification decoction (ADD) treatment group (N=62) and a non-ADD treatment group (N=78), according to whether they consumed ADD after chemotherapy or not. Furthermore, drug resistance of the MDA-MB-231/ADR cell line in response to gemcitabine (GEM), adriamycin (ADM), oxaliplatin (OXA), and cisplatin (DDP) was evaluated, and glycolytic potential of MDA-MB-231/ADR cells was determined after astragaloside IV treatment or si-hsa_circ_0001982/miR-206 inhibitor/miR-613 inhibitor transfection. Results: TNBC patients receiving ADD adjuvant therapy after chemotherapy, with decreased serum level of hsa_circ_0001982 and increased serum level of miR-206/miR-613 as relative to non-ADD treatment group ( P < 0.05), were less likely to relapse than TNBC population not undergoing ADD treatment ( P < 0.05). In addition, GEM/ADM/OXA/DDP-resistance and glycolysis of MDA-MB-231/ADR cell line were debilitated after exposure to astragaloside IV or transfection by si-hsa_circ_0001982 ( P < 0.05). Nonetheless, miR-206/miR-613 inhibitor transfection reversed inhibitory effects of si-hsa_circ_0001982 and astragaloside IV on glycolysis and MDR of MDA-MB-231/ADR cell line ( P < 0.05). Conclusion: Astragaloside IV undermined MDR and glycolysis of MDA-MB-231/ADR cell line by blocking hsa_circ_0001982-miR-206/miR-613 axis. Keywords: triple-negative breast cancer, astragaloside IV, hsa_circ_0001982, miR-206, miR-613, multi-drug resistance, glycolysis