力达霉素诱导人多发性骨髓瘤RPMI8226细胞凋亡和周期阻滞

Lidamycin iduces cell apoptosis and cell cycle arrest of human multiple myeloma RPMI 8226 cells

目的研究力达霉素(LDM)的抗骨髓瘤作用,并探讨抗骨髓瘤的作用机制。方法处于对数增殖期人多发性骨髓瘤细胞RPMI 8226细胞随机分为空白对照组及0.1、0.5和1 nmol/L LDM组,用MTS法和流式细胞术检测细胞增殖率、细胞周期分布和凋亡情况,采用Western blot法检测凋亡相关蛋白和周期相关蛋白的表达量。结果细胞培养48 h后,不同浓度LDM组细胞增殖数显著低于空白对照组数(P<0.05),LDM组S期和G2/M期的细胞数显著高于对照组数(P<0.05),细胞凋亡率显著高于空白对照组数(P<0.05),LDM的增殖抑制作用和凋亡诱导作用呈剂量依赖性。不同浓度LDM组细胞caspase-3、caspase-7、caspase-9和poly ADP-ribose polymerase(PARP)的蛋白被切割明显高于对照组(P<0.05),P21和P27蛋白的表达量明显高于对照组数(P<0.05)。结论 LDM能诱导人多发性骨髓瘤细胞RPMI 8226细胞凋亡并诱导S期和G2/M期阻滞,其诱导凋亡和周期阻滞的机制有待于进一步深入研究。

Objective To investigate the effect of lidamycin（ LDM） against multiple myeloma and its mechanism.Methods The human multiple myeloma RPMI 8226 cells in logarithm growth phase were selected and were randomly divided into control group,0. 1,0. 5 and 1 nmol / L LDM groups. MTS assay was used to detect the proliferation rate of RPMI 8226 cells and the flow cytometry method was used to analyze the distribution of cell cycle and cell apoptosis in various groups. The expression levels of protein associated with apoptosis and cell cycle were detected by Western blotting method. Results After 48 h cell culture,the cell proliferation rate in LDM groups was lower than those in control group（ P 0. 05）. The number of S phase and G2/ M phase cells in LDM groups was higher than those in control group（ P 0. 05）. The cell apoptosis rate in LDM groups was higher than those in control group（ P 0. 05）. The expressions of cleaved caspase-3,caspase-7,caspase-9 and poly ADP-ribose polymerase（ PARP） in LDM group were higher than those in control group（ P 0. 05）. The expression of P21 and P27 in LDM group were higher than those in control group（ P 0. 05）. Conclusions LDM can induce apoptosis by increasing the levels of cleaved caspase-3,caspase-7,caspase-9,and PARP in cells and LDM can induce the S phase and G2/ M phase arrest by increasing the levels of P21 and P27 in human multiple myeloma RPMI 8226 cells.