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淋巴细胞特异性蛋白-1(LSP1)在部分多发性骨髓瘤中表达升高,但其在肿瘤中的作用仍知之甚少.研究了LSP1在多发性骨髓瘤中抗新型抗肿瘤药物万珂(Bortezomib)诱导细胞凋亡的作用及机制.筛选LSP1高表达和低表达的多发性骨髓瘤细胞IM9和KAS6作为实验模型.应用RNA干扰基因沉默IM9细胞中的LSP1,或在KAS6细胞中转染LSP1表达质粒,用Bortezomib等化疗药物处理细胞后,PI/Annexin V染色并用流式细胞仪检测和分析细胞凋亡率.同时RT-PCR方法检测和分析被LSP1所影响的重要细胞凋亡相关基因的变化.结果发现,LSP1在多发性骨髓瘤细胞IM9和KAS6中差异性表达高和低,与Bortezomib诱导的细胞凋亡效率密切相关.利用RNA干扰敲低IM9细胞中LSP1,可显著增强IM9对Bortezomib的敏感性,同时在KAS6中转染LSP1表达质粒,可降低Bortezomib诱导的细胞凋亡.对部分重要凋亡基因的RT-PCR检测发现,LSP1可诱导BCL-xl基因表达,同时抑制p53表达.因此,发现LSP1可通过调节凋亡基因的表达促进肿瘤的抗药性.
The expression of lymphocyte specific protein-1 (LSP1) is elevated in some multiple myeloma patients, but its role in the tumor is still poorly understood. LSP1 is an anti-neoplastic anti-tumor agent in multiple myeloma, Bortezomib induced apoptosis and its mechanism.METHODS Multiplex myeloma cells (IM9 and KAS6) with high expression and low expression of LSP1 were selected as experimental models.The RNA interference gene was used to silence LSP1 in IM9 cells or LSP1 in KAS6 cells After the cells were treated with Bortezomib and other chemotherapeutic drugs, PI / Annexin V staining and flow cytometry were used to detect and analyze the apoptosis rate.Meanwhile RT-PCR was used to detect and analyze the expression of important apoptosis-related genes The results showed that LSP1 was highly differentially expressed in multiple myeloma cells IM9 and KAS6 and was closely related to the efficiency of Bortezomib induced apoptosis.It was found that LSP1 knockdown of LSP1 in IM9 cells significantly enhanced the inhibitory effect of IM9 on Bortezomib , And at the same time transfected with LSP1 expression plasmid in KAS6 can reduce Bortezomib induced apoptosis.It was found by RT-PCR analysis of some important apoptotic genes that LSP1 could induce BCL-xl gene expression, Inhibited the expression of p53.Therefore, LSP1 was found to promote tumor drug resistance by regulating the expression of apoptotic genes.