Xbp-1基因沉默对硼替佐米诱导人多发性骨髓瘤细胞凋亡的影响

本研究旨在探讨xbp-1基因沉默对硼替佐米诱导骨髓瘤细胞株NCI-H929(H929)凋亡的影响。通过小发夹RNA(shRNA)干扰xbp-1基因表达,采用Annexin V-FITC/PI双染流式细胞术检测靶细胞凋亡率,采用Wes-ternblot检测XBP-1蛋白水平。结果表明:通过慢病毒载体PLL3.7介导的xbp-1 shRNA表达,能有效抑制H929细胞XBP-1蛋白表达,xbp-1 shRNA表达细胞的凋亡率显著高于对照组[(10.13±0.61)%vs(2.5±0.2)%,p0.05];经硼替佐米处理后,xbp-1基因功能缺陷的H929细胞的凋亡率显著高于空载体组[(45.07±1)%vs(2.73±0.25)%,p0.05]。结论:xbp-1基因沉默能够显著增强硼替佐米对多发性骨髓瘤细胞的促凋亡活性。

Effects of xbp-1 Gene Silencing on Bortezomib-induced Apoptosis in Human Multiple Myeloma Cells

This study was purposed to investigate the effect of xbp-1 gene silencing on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929（H929）.After xbp-1 gene expression was interfered by small hairpin RNA,the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining,and the expression level of XBP-1 protein was detected by Western blot.The results showed that XBP-1 protein level of H929 cells was inhibited effectively by the PLL3.7 lentiviral vector mediated expression xbp-1 shRNA.The apoptosis rate was significantly higher in xbp-1 shRNA-expressing cells than in untreated control group [（10.13±0.61）% vs（2.5±0.2）%,p0.05].After treatment with bortezomib,the apoptosis rate of XBP-1 protein functionally deficient H929 cells was significantly higher than those in vector control group[（45.07±1）% vs（19.53±0.8）%,p0.05].It is concluded that xbp-1 gene silencing can significantly enhance the pro-apoptotic activity of bortezomib in multiple myeloma cells.