RhoB抑制慢性粒细胞白血病细胞的生长

Suppressive effect of RhoB on CML cells proliferation

目的:研究RhoB对慢性粒细胞白血病(chronic myeloid leukemia,CML)细胞增殖能力的影响。方法:用PCR扩增RhoB编码区并构建几种RhoB脂类修饰突变体。以慢病毒为载体携带RhoB及其突变体在CML细胞中过表达后,检测细胞增殖能力,并分析细胞的周期进程。结果:过表达RhoB能抑制MEG-01细胞及CML患者CD34+细胞的增殖;脂类修饰缺失的RhoBC193G不能抑制CML细胞的增殖;单独进行法尼基(F)修饰和单独进行牻牛儿基牻牛儿基(GG)修饰的RhoB均可抑制CML细胞的增殖;过表达RhoB及其单种脂类修饰变体将CML细胞阻滞于G2/M期。结论:RhoB需要F或GG类型的脂类修饰才能抑制CML细胞的生长并将CML细胞阻滞于G2/M期。

Objective： To study the effects of RhoB on the proliferation of chronic myeloid leukemia（CML） cells. Methods： Wild type RhoB and its lipid modification variants were amplified by PCR; lentiviral vectors were constructed to overexpress RhoB and its variants in CML cells ; effect on the growth of CML cell and the alteration of cell cycle were analyzed. Results： Overexpression of RhoB in MEG-01 and CD34~ cells from CML patients reduced their proliferation. The lipid modification deficient variant RhoBC193G could not inhibit the growth of CML cells. Both farnesylated （ F ） and geranylgeranylated （ GG ） RhoB （ RhoB- F and RhoB- GG ） decreased the proliferation ability of CML cells. RhoB, RhoB-F and RhoB-GG transduced CML cells resided more at G2/M phase compared with control or RhoBCI93G transducted cells. Conclusion： RhoB required lipid modification to suppress the growth of CML cells, which is correlated with the arrest of cells at G2/M.