摘要
目的研究白藜芦醇对多发性骨髓瘤细胞体外抗癌作用,探讨其抗癌作用的分子机制。方法用MTT法检测白藜芦醇对骨髓瘤细胞系RPMI-8226和KM3增殖的影响;Annexin-V/PI双标流式细胞术检测白藜芦醇对RPMI-8226细胞凋亡的影响;PI单标流式细胞术测定白藜芦醇对RPMI-8226、KM3细胞DNA分布的影响;Western-blotting方法检测白藜芦醇对RPMI-8226细胞Bcl-2、Bax、XIAP、c-IAP-1、c-IAP-2蛋白表达的影响。结果白藜芦醇对RPMI-8226和KM3细胞具有明显的增殖抑制作用,其抑制增殖作用呈时效和量效关系。25~100μmol/L白藜芦醇作用24h可诱导RPMI-8226细胞凋亡,100μmol/L作用24h时KM3细胞凋亡率达(26.5±2.7)%。白藜芦醇处理组RPMI-8226及KM3细胞周期均发生变化,细胞周期被阻滞于S期和G0/G1期。白藜芦醇以时间依赖方式下调抗凋亡蛋白Bcl-2、XIAP、c-IAP-1、c-IAP-2的表达,并可上调促凋亡蛋白Bax的表达,但白藜芦醇对各蛋白作用的动力学不同。结论白藜芦醇可通过调控细胞周期进程、诱导细胞凋亡而有效抑制骨髓瘤细胞增殖,其诱导细胞凋亡与调节Bcl-2和IAP家族蛋白的表达有关。
Objective To investigate the anticancer activities of resveratrol on human multiple myeloma (MM) cells and their molecular mechanisms involved. Methods The effect of resveratrol on the growth of MM cell lines RPMI-8226 and KM3 were studied through MTT assay. The effect of resveratrol on the apoptosis of RPMI-8226 cells were studied by combined Annexin-V protein iodide staining. The effect of resveratrol on the cell cycle of RPMI-8226 and KM3 cells were studied by a propidium iodide method. The effect of resveratrol on the expression was studied by Western blotting analysis. Results of Bcl-2, Bax, XIAP, c-IAP-1, and c-IAP-2 protein Resveratrol inhibited the proliferation of RPMI-8226 and KM3 ceils in a time- and dose-dependent manner. Treatment with 25-100 μmol/L resveratrol for 24 h induced apoptosis of RPMI-8226 cells and the apoptosis rate reached (26.5±2.7)% at concentration of 100 μmol/L. Flow cytometric analyses showed that RPMI-8226 and KM3 cells treated with resveratrol were accumulated in G0/G1 and S phase in the cell cycle, the ratio of cells in G2/M phase was decreased at 24 h treatment. The expression of Bcl-2, XIAP, c-IAP-1, and c-IAP-2 protein was decreased in a time- dependent manner with different kinetics in MM cells treated with resveratrol, while Bax protein was increased. Conclusion Resveratrol is able to inhibit the proliferation of MM ceils by regulating the cell cycle and inducing the cell apoptosis. Regulating the expression of Bcl-2 and IAP family members may suggest an involvement in the resveratrol-induced apoptosis.
出处
《中草药》
CAS
CSCD
北大核心
2007年第1期80-84,共5页
Chinese Traditional and Herbal Drugs