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目的:探讨姜黄素对骨髓瘤细胞株MM1.R细胞中HSP9的抑制及增强硼替佐米效应的分子机制。方法:MTT比色法观察不同浓度姜黄素单用和联用0.01 mmol/L硼替佐米对MM1.R细胞的生长抑制作用;用流式细胞仪(Annexin-V和PI标记)分析细胞凋亡;Western-blot方法检测caspase 3,caspase 9蛋白表达,NF-κB蛋白,HSP-90蛋白表达变化。结果:姜黄素单用对MM1.R细胞有一定程度的生长抑制和诱导凋亡作用。而联用0.01 mmol/L硼替佐米后,其浓度依赖作用更明显。而且Western-blot显示两药联用后,上调caspase 3,caspase 9,和下调NF-κB,HSP 90作用更明显,与凋亡和生长抑制呈相关性。结论:姜黄素增加MM1.R细胞对硼替佐米的敏感性,诱导凋亡发生,可能是通过下调NF-κB蛋白和HSP 90蛋白活性实现的。
OBJECTIVE: To investigate the molecular mechanism of curcumin inhibiting HSP9 in myeloma MM1.R cells and enhancing the effect of bortezomib. Methods: MTT assay was used to observe the inhibitory effect of curcumin at different concentrations on the growth of MM1.R cells in combination with 0.01 mmol / L bortezomib. The apoptosis was analyzed by flow cytometry (Annexin-V and PI) The protein expression of caspase 3, caspase 9, NF-κB and HSP-90 were detected by Western-blot. RESULTS: Curcumin alone had a certain degree of growth inhibition and induction of apoptosis on MM1.R cells. The combination of 0.01 mmol / L bortezomib, its concentration-dependent effect is more obvious. Moreover, Western-blot showed that the combination of the two drugs increases the expression of caspase 3, caspase 9, and down-regulates NF-κB. The effect of HSP 90 is more obvious, which is correlated with the apoptosis and growth inhibition. CONCLUSION: Curcumin increases the sensitivity of bortezomib to MM1.R cells and induces apoptosis, possibly through down-regulation of NF-κB protein and HSP90 protein activity.