共同抑制mTORC2和热休克蛋白90对多发性骨髓瘤细胞凋亡的影响

OBJECTIVE: To explore apoptosis of multiple myeloma (MM) cells and its mechanism by the combined inhibition of mTORC2 signaling pathway and heat shock protein 90. METHODS: The effects of Rapamycin, 17-AAG and the combination on proliferation of MM cell lines U266 and KM3 were assessed using MTT at different time points (0, 8, 24, 48 hour). Cell apoptosis and cell cycle distribution were measured by flow cytometry. The specific proteins p-AKT(ser473), p-AKT(thr450), p-S6(S235/236) and AKT were detected by Western blotting. RESULTS: Rapamycin, 17-AAG and the combination suppressed the proliferation of MM cell lines U266 and KM3, especially the combination of Rapamycin and 17-AAG synergistically inhibited the proliferation (P<0.05); Rapamycin induced G(1) arrest both at 24 and 48 hours, 17-AAG also induced G(1) arrest, especially at 48 hours (P<0.01); Rapamycin, 17-AAG alone decreased the expression of AKT and induced MM cell apoptosis to some extent (P<0.01); Chronic rapamycin treatment inhibited mTORC2; Inhibition of both mTORC2 and chaperon pathways degraded AKT and induced MM cell apoptosis, which was significantly higher than that of any single agent (P<0.01). CONCLUSION: Inhibition of both mTORC2 and chaperon pathways decreased the expression of AKT to induce apoptosis of MM cells in vitro.