单核细胞趋化因子及钟声蛋白样受体在卡介苗灌注膀胱局部抗肿瘤免疫反应中的表达

Expression of monocyte chemotactic protein-1 and toll-like receptors in bacillus Calmette-Guerin induced immunol responses to human bladder cancer

目的:观察行卡介苗(BCG)膀胱灌注治疗后,膀胱肿瘤中MCP-1,钟声蛋白样受体(TLR4,TLR2),以及核转录因子кB(NFкB)的表达,探讨MCP-1在BCG抗肿瘤中的作用及其可能的机制。方法:分别提取标本组织中的总RNA,用MCP-1,TLR4,TLR2,NFкB的寡核苷酸引物进行逆转录聚合酶链反应(RT-PCR)技术扩增,产物经琼脂糖凝胶电泳后,用凝胶成像系统检测原发膀胱移行细胞癌标本、正常膀胱黏膜以及BCG灌注治疗后膀胱移行细胞癌复发标本中MCP-1,TLR4,TLR2,NFкB mRNA的表达。结果:在TURBT标本中,经膀胱BCG灌注治疗后,复发的膀胱移行细胞癌标本中MCP-1,TLR4,TLR2,NFкB mRNA表达增强。结论:经BCG灌注治疗后,其肿瘤标本中MCP-1,TLR4,TLR2,NFкB mRNA的表达增强,提示BCG的抗瘤机制可能包括TLR4,TLR2,诱导NFкB信号系统的激活导致肿瘤局部产生MCP-1的升高,进而起到抗肿瘤作用。

Objective：To explore the expression of Toll-like receptors（TI.R2 , TLR4 ）, nuclear factor kappa B （NFkB） and MCP-1 in BCG-induced immunol response ＂to bladder cancer, furtherrnore ＂to discuss ＂the procedure and mechanism production of MCP-1. Methods：There were total 58 samples, in which 10 urologic tumor-free patients were selected as controls, 28 patients with superficial bladder cancer（grade. T1;stages2--3）who had previ- ously undergone transurethral resection（TUR） received intravesical BCG （bacillus Calmette-Guerin） treatment, and 20 patients with primary cancer did not receive BCG. The total RNA of each sample was extracted. RT-PCR procedure was conducted using primer of MCP-1, TLR-2, TLR-4, NFkB（Premega）, and products were analyzed with agarose gels electrophoresis. Results：The expressions of MCP-1 ,TLR-2 ,TLR-4 and NFkB were increased in BCG-treated bladder cancer samples, compared with untreated bladder cancer samples and urologic tumor-free samples. Conclusions： The expressions of MCP-1 ,TLR-2,TLR-4 and NFkB were increased in BCG-treated bladder cancer samples. Expression of MCP-1 may be depended on TLR2 and TLR4 activating NFkB. MCP-1 expression up-regulation was partially involved in antitumor mechanism of BCG.