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

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

Acknowledgments and Fundings

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (No. 81703881), Minhang District Science and Technology Commission Project(2019MHZ030)and High Level Key Specialist Doctors under the Medical Teaching Research Collaborative Health Service System in Minhang District (No. 2020MZYS02).

Disclosure

The authors report no conflicts of interest in this work.