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目的:观察白介素-6(IL-6)对伯基特淋巴瘤(BL)Raji细胞和弥漫大B细胞淋巴瘤(DLBCL)OCI-LY8细胞生长的影响,探讨信号转导子与转录活化-3(STAT3)及基质金属蛋白酶组织抑制因子-1(TIMP-1)分子在BL和DLBCL中发生发展的作用及其相互关系。方法:用不同浓度的IL-6(0、50、100、150及200μg/L)分别培养Raji细胞和OCI-LY8细胞24h、48h及72h(分别为对照组和不同浓度IL-6试验组),用MTT法检查2株细胞生长情况,用RT-qPCR检测培养48h时2株细胞STAT3、TIMP-1的mRNA表达,用Westernblot检测100μg/LIL-6培养48h时Raji细胞的STAT3、p-STAT3及TIMP-1蛋白的表达,流式细胞技术检测100μg/LIL-6培养48h时2株细胞的细胞周期变化。结果:与相应的对照组比较,不同浓度IL-6试验组2株细胞在A490nm处OD值明显降低,呈现药物浓度依赖关系(P<0.01);2株细胞内的STAT3,TIMP-1的mRNA表达明显升高(P<0.05),呈现出药物浓度依赖关系(P<0.05),2株细胞内TIMP-1与STAT3的mRNA表达呈正相关关系(r=0.982,P=0.018);IL-6组Raji细胞中p-STAT3、STAT3和TIMP-1蛋白表达增高;IL-6组Raji和OCI-LY8细胞的G1期细胞都明显减少、S期细胞明显增多(P<0.05),G2M期的Raji细胞无明显变化而OCI-LY8细胞则明显增多(P=0.037)。结论:IL-6对Raji细胞和OCI-ly8细胞生长有明显作用,STAT3活化及其下游靶基因TIMP-1的上调表达可能是IL-6影响2株细胞生长的重要分子机制。
OBJECTIVE: To investigate the effects of interleukin-6 (IL-6) on the growth of Burkitt’s lymphoma (BL) Raji cells and diffuse large B-cell lymphoma (DLBCL) OCI-LY8 cells and to explore the roles of signal transducer and activator of transcription-3 (STAT3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in BL and DLBCL. Methods: Raji cells and OCI-LY8 cells were cultured with different concentrations of IL-6 (0,50,100,150 and 200μg / L) for 24h, 48h and 72h respectively (control group and different concentrations of IL-6 test group) , The growth of 2 cell lines was examined by MTT assay. The mRNA expression of STAT3 and TIMP-1 was detected by RT-qPCR in two cell lines at 48h. The STAT3 and p-STAT3 expression of Raji cells were detected by Western blot after treated with 100μg / L IL-6 And TIMP-1 protein expression. Flow cytometry was used to detect the cell cycle changes of 2 cells cultured in 100μg / L IL-6 for 48h. Results: Compared with the corresponding control group, the OD values of A490nm and IL-6 in two different concentrations of IL-6 significantly decreased (P <0.01). The mRNA and protein expressions of STAT3 and TIMP-1 (P <0.05). There was a positive correlation between mRNA expression of TIMP-1 and STAT3 (r = 0.982, P = 0.018), IL-6 The expression of p-STAT3, STAT3 and TIMP-1 protein in Raji cells increased significantly. The cells in G1 phase in Raji and OCI-LY8 cells in IL-6 group were significantly decreased, the cells in S phase were significantly increased (P <0.05) Of Raji cells did not change significantly while OCI-LY8 cells were significantly increased (P = 0.037). CONCLUSION: IL-6 has a significant effect on the growth of Raji cells and OCI-ly8 cells. The activation of STAT3 and upregulation of its downstream target gene TIMP-1 may be the important molecular mechanism of IL-6 on the growth of 2 cells.