TLR4/NF-κB在人结肠癌细胞SW620中的表达及CRX-526的抑制作用  

TLR4/NF-κB Signaling Pathway in the Human Colon Cancer SW620 Cells and Effect of CRX-526 on Growth of Mouse Xenograft

作　　者：黄宏耀[1] 刘方方[1] 张秋莹[1] 刘国政[1] 钱进[1] 

机构地区：[1]湖北省随州市中心医院检验,随州441300

出　　处：《微循环学杂志》2013年第3期3-6,F0002,I0001,共6页Chinese Journal of Microcirculation

基　　金：湖北省自然科技基金一般项目(2011CDC041)

摘　　要：目的:利用脂多糖(LPS)刺激人结肠癌SW620细胞,观察Toll样受体4(TLR4)和核因子-κB(NF-κB)(p65)mRNA和蛋白表达,探讨TLR4拮抗剂CRX-526对肿瘤的抑制作用。方法:用LPS刺激培养的人结肠癌SW620细胞(LPS刺激组),检测其与未经刺激的SW620细胞(无刺激组)TLR4和NF-κB(p65)的mR-NA和蛋白表达水平差异,以及两组炎症因子白细胞介素-6(IL-6)和IL-8的表达变化。同时利用SW620细胞皮下注射建立裸鼠移植瘤,并用TLR4拮抗剂CRX-526进行多点注射,观察移植瘤的体积及肿瘤组织中TLR4、NF-κB(p65)表达变化。结果:与无刺激组相比,LPS刺激组SW620细胞中TLR4、NF-κB(p65)、IL-6和IL-8表达明显上调(P<0.05)。抑制组肿瘤体积(271.25±49.44)mm3明显小于非抑制组(423.32±31.28)mm3,抑制组TRL4和NF-κB(p65)mRNA和蛋白的表达显著低于非抑制组(P均<0.05)。结论:研究TLR4/NF-κB信号通路在结肠癌中的作用及作为治疗靶点,对结肠癌临床干预有重要价值。Objective:To observe mRNA and protein expression of TLR4 / NF-κB in human colon cancer SW620 cells induced by lipopolysaccharide(LPS) and explore the potential therapeutic value about TLR4 antagonist CRX-526 on colon cancer. Method:Using LPS stimulate human colon cancer SW620 cells(stimulated group), we detected both mRNA and protein of TLR4 and NF-κB(p65) expression differences between SW620 cells that stimulated and not(unstimulated group), and the expression of IL6 and IL8. Meanwhile, we established cancer xenograft model nude mice using SW620 cells to inject nude mice by multiple sites subcutaneously, and observed changes of the tumor volume and TLR4,NF-κB (p65),IL6 and IL8 in tumor tissue. Results:Compared with control, TLR4,NF-κB (p65),IL6,IL8 expression were obviously increased in SW620 cells of experimental group(P<0.05). And the tumor volume of inhibitor experimental group (271.25±49.44)mm3 was larger less clearly than no inhibitor group (423.32±31.28)mm3(P<0.05), and the expression of the protein and mRNA of TRL4,NF-κB (p65) in inhibitor group were less than no inhibitor group. Conclusion:TLR4/NF-κB signaling pathway plays an important role in colon cancer and it may be a therapeutic target for clinical therapeutic intervention.

关 键 词：结肠癌 SW620 脂多糖 TLR4 NF-ΚB 炎症反应 

分 类 号：R735.35[医药卫生—肿瘤]