李品浩,杨文秀,陈琴,裴媛媛
LI Pinhao,YANG Wenxiu,CHEN Qin,PEI Yuanyuan

• 1:贵州医科大学病理学教研室

摘要(Abstract)：

目的:研究AG490对伯基特淋巴瘤(BL)Raji细胞和弥漫大B细胞淋巴瘤(DLBCL)OCI-LY8细胞生长的影响及分子机制。方法:用不含AG490(对照组)和不同浓度(25、50、75及100 mg/L)AG490(试验组)分别培养Raji细胞和OCI-LY8细胞24、48及72 h,用MTT法检查2株细胞的代谢生长情况,RT-q PCR检测对照组和各试验组培养48 h时2株细胞STAT3、TIMP-1的m RNA表达;用Western blot检测AG490 50 mg/L培养48 h时Raji细胞的STAT3、p-STAT3及TIMP-1蛋白的表达,流式细胞术检测2株细胞的细胞周期变化。结果:在2株细胞中加入AG490后,细胞生长较对照组明显减弱(P<0.05);与相应对照组比较,AG490试验组的Raji细胞和OCI-LY8细胞的G1期细胞都明显增多(P<0.05),处于S期的Raji细胞无明显改变、而OCI-LY8细胞则明显减少(P<0.05),G2-M期的Raji细胞明显减少(P<0.05)、G2-M期的OCI-LY8细胞亦有减少的趋势;STAT3和TIMP-1的m RNA表达明显降低,且呈现出药物浓度依赖关系(P<0.05);2株细胞内TIMP-1与STAT3的m RNA表达呈正相关关系(Raji r=0.744,P=0.034;OCI-LY8 r=0.984,P=0.000);AG490组Raji细胞中p-STAT3、STAT3和TIMP-1蛋白表达较对照组明显降低。结论:AG490对Raji细胞和OCI-ly8细胞生长有明显抑制作用,TIMP-1的表达可能与SATA3的活化有关,STAT3活化及其下游靶基因TIMP-1的上调表达可能是AG490影响2株细胞生长的重要分子机制。
Objective: To investigate the effect and molecular mechanism of AG490 on the growth of Burkitt lymphoma( BL) cell line Raji and Diffuse large B cell lymphoma( DLBCL) cell line OCILY8. Methods: Raji and OCI-LY8 cells were cultured by non AG490( control group) and varied concentration AG490 experiment group(25,50,75 and 100 mg / L) for 24,48 and 72 h. Cell viability was assayed by MTT. The expressions of STAT3 and TIMP-1 at m RNA level were detected by real time RT-PCR. STAT3,p STAT3 and TIMP-1 protein expression of Raji cell cultivated by AG490 50 mg / L for 48 h were detected by Western blotting. 2 strains of cell cycle was examined by flow cytometry.Results: Comparing with corresponding control group,cell viability was decreased in the two cell strains treated with AG490( P < 0. 05). The opposite change was found in AG490 experiment group,Raji cells and OCI-LY8 cells of phase G1 had a trend to significantly increase( P < 0. 05); the OCILY8 cells of phase S decreased significantly( P < 0. 01),while Raji cells had no obvious change( P <0. 01);Raji cells of phase G2-M decreased significantly( P < 0. 01),OCI-LY8 cells showed tendency of reducing; m RNA expression of STAT3 and TIMP-1 reduced significantly and indicated concentration-dependence relationship( P < 0. 05); m RNA expressions of STAT3 and TIMP-1 in 2 strains of cell presented positive correlation( Raji r = 0. 744,P = 0. 034; OCI-LY8 r = 0. 984,P = 0. 000); pSTAT3,STAT3 and TIMP-1 protein expression of AG490 group were obviously reduced compared with those of control group. Conclusions: AG490 obviously inhibits the growth of Raji and OCI-LY8 cells.The expression of TIMP-1 may be associated with STAT3 activation. The activation of STAT3 and upregulated expression of TIMP-1 might be the essential molecular mechanism of AG490 influence over the growth of 2 strains of cells.

关键词(KeyWords)： 淋巴瘤,B细胞;伯基特淋巴瘤;信号转导和转录激活因子;基质金属蛋白酶组织抑制因子-1;AG490;生长抑制物
lymphoma;B cell;Burkitt lymphoma;single transducer and transcription activator-3;tissue inhibitors of metalloproteinase-1;AG490;growth inhibitor

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(No.81160299);; 贵州省优秀人才省长基金(No.2011.125)

作者(Author): 李品浩,杨文秀,陈琴,裴媛媛
LI Pinhao,YANG Wenxiu,CHEN Qin,PEI Yuanyuan

DOI: 10.19367/j.cnki.1000-2707.2016.02.003

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