Ginsenoside Rg1 inhibits multiple myeloma and overcomes bortezomib resistance through AMPK-mTOR pathway.

Background: The resistance of multiple myeloma (MM) to bortezomib (BTZ) has brought multiple challenges to its clinical use. Numerous ginsenosides have potential anti-tumor effects, however, the research on the role of Rg1 in MM has not been reported. Objective: To examine the inhibitory impact of Rg1 on the growth of MM and reduce the drug resistance of MM to BTZ through Methods: BTZ drug-resistant cell line RPMI8226R was constructed. Mouse tumor-bearing model was developed by abdominal subcutaneous injection of MM cells. MM cells were treated with AMPK inhibitor Compound C or autophagy inhibitor Chloroquine together with Rg1. RPMI8226R cells were treated with BTZ and Rg1. Cell multiplication was detected using Methylthiazolyldiphenyl-tetrazolium bromide assay. Apoptosis was assessed using flow cytometry. Immunofluorescence assay was employed to assess the autophagy markers LC3. Western blot was utilized to assess the protein expression. Immunohistochemistry was used to detect cell proliferation and apoptosis in tumor tissues. Results: Conclusion: Rg1 has significant anti-MM effect and can overcome BTZ resistance, and its potential mechanism is related to the regulation of autophagy induced by AMPK-mTOR pathway. Rg1 is a promising adjuvant drug for the treatment of MM.