Momordica protein MAP30 promotes apoptosis and autophagy via AKT/mTOR pathway in multiple myeloma cell / 中国肿瘤生物治疗杂志

ABSTRACT

@#Objective: To investigate the role of momordica protein MAP30 in multiple myeloma (MM) and the possible mechanism. Methods: Human myeloma RPMI-8226, NCI-H929 and U266 cells were treated with MAP30 at different concentration (1-10 μmol/L) and then the proliferation rates of cells were detected by CCK-8 assay.Annexin V/PI flow cytometry was used to evaluate the apoptosis rate of myeloma cells, and the expressions of apoptosis-related protein (PARP), autophagy-related proteins (LC3II, P62) andAkt/mTOR pathway-related proteins in multiple myeloma cells were also detected via Wb. The changes in cell proliferation, apoptosis and autophagy after the treatment of MAP30 combined with autophagy agonist rapamycin (Rap) or autophagy inhibitor bafilomycin (Baf) were observed by CCK-8, flow cytometry and Wb, respectively. Results: MAP30 (1-10 μmol/L) inhibited the proliferation of myeloma cells in a time- and dose-dependent manner (P<0.05 or P<0.01). With MAP30 acting on myeloma cells alone, the apoptosis and autophagy of MM cells, as well as the expression of PARP cleavage and LC3II increased while the expression of P62 decreased significantly (all P< 0.05 or P<0.01). After being treated with MAP30+Baf, compared with MAP30 treatment alone, the cell proliferation was remarkably enhanced while cell apoptosis and cell autophagy were suppressed, besides, the expression of PARP cleavage and LC3II were decreased and P62 level was augmented (all P<0.05 or P<0.01). Conversely, after being treated with MAP30+Baf, compared with MAP30 treatment or Baf treatment alone, cell proliferation and P62 level were reduced, while apoptosis and autophagy as well as the expressions of PARP cleavage and LC3II level were increased (all P<0.05 or P<0.01). The expressions of p-AKT and p-mTOR were significantly reduced with the effect of MAP30 on myeloma cells (all P<0.05). Conclusion: MAP30 can promote the apoptosis and autophagy of myeloma cells throughAKT/mTOR pathway, which may provide a new therapeutic strategy for treatment of multiple myeloma.