TLR4/NF-κB信号通路在瘢痕癌组织中的表达及TAK-242对瘢痕癌细胞影响的研究  

Expression of TLR4/NF-κB signaling pathway in scar cancer tissues and effect of TAK-242 on scar cancer cells

作　　者：霍文亮 田小瑞[1] 张锦若 梁钢[3] 王建明 白培懿 刘翠花 董玉莹 徐宽宽 孟艳斌 HUO Wenliang;TIAN Xiaorui;ZHANG Jinruo;LIANG Gang;WANG Jianming;BAI Peiyi;LIU Cuihua;DONG Yuying;XU Kuankuan;MENG Yanbin(Taiyuan Iron&Steel(Group)Co.,LTD.General Hospital(The Sixth Hospital of Shanxi Medical University,Shanxi Burn Treatment Center),Taiyuan 030009,China;College of Science,China Pharmaceutical University,Nanjing 211100,China;Department of Pathology,The First Hospital of Shanxi Medical University,Taiyuan 030003,China)

机构地区：[1]太原钢铁(集团)有限公司总医院,暨山西医科大学第六医院、山西省烧伤救治中心,山西省太原市030009 [2]中国药科大学理学院,江苏省南京市211100 [3]山西医科大学第一医院病理科,山西省太原市030003

出　　处：《组织工程与重建外科》2025年第1期14-19,共6页Journal of Tissue Engineering and Reconstructive Surgery

基　　金：山西省卫生健康委“四个一批”科研基金项目(2023XM051);山西省卫生健康委科研课题基金项目(2024183)。

摘　　要：目的分析皮肤瘢痕癌组织中Toll样受体4(TLR4)及核因子kappa B(NF-κB)的表达,研究TLR4抑制剂TAK-242对瘢痕癌细胞的影响。方法收集正常皮肤组织、增生性瘢痕组织及瘢痕癌组织各20例,采用免疫组织化学及逆转录聚合酶链式反应(RT-PCR)检测TLR4、NF-κB蛋白及mRNA的表达情况,分析TLR4、NF-κB的表达与患者性别、年龄、肿瘤分化程度等临床病理因素之间的关系。体外原代培养瘢痕癌细胞,采用TLR4抑制剂TAK-242作用于瘢痕癌细胞,MTT法检测细胞增殖活性,蛋白印迹实验检测TLR4、NF-κB、MMP9、TGF-β1蛋白的表达情况。结果与对照组相比,瘢痕组织及瘢痕癌组织中TLR4、NF-κB蛋白及mRNA的表达显著增高(P<0.05);与瘢痕组织相比,瘢痕癌组织中TLR4、NF-κB蛋白及mRNA的表达显著增高(P<0.05)。瘢痕癌组织中TLR4及NF-κB的表达与肿瘤分化程度有关(P<0.05);经TLR4抑制剂TAK-242干预后,瘢痕癌细胞增殖活性显著降低(P<0.05),TLR4、NF-κB、MMP9、TGF-β1蛋白表达下调(P<0.05)。结论TLR4/NF-κB信号通路参与了瘢痕组织癌变的病理过程,TLR4抑制剂TAK-242可抑制瘢痕癌增殖,有望成为瘢痕组织治疗的新靶点。Objective To analyze the expression of Toll like receptor 4(TLR4)and nuclear factor kappa B(NF-κB)in scar cancer tissues,and to investigate the effect of TLR4 inhibitor TAK-242 on scar cancer cells.Methods 20 cases of normal skin tissue,20 cases of hypertrophic scar tissue,and 20 cases of scar cancer tissue were collected.Immunohistochemistry and reverse transcription polymerase chain reaction(RT-PCR)were used to detect the expression of TLR4 and NF-κB protein and mRNA.The relationship between the expression of TLR4,NF-κB and clinical pathological factors such as patient gender,age,and tumor differentiation degree was analyzed.Scar cancer cells were cultured in vitro and treated with TLR4 inhibitor TAK-242.Cell proliferation activity was detected by MTT assay,and the expression of TLR4,NF-κB,MMP9,and TGF-β1 proteins was detected by Western blot assay.Results Compared with the control group,the expression of TLR4,NF-κB protein and mRNA in scar tissue and scar cancer tissue was significantly increased(P<0.05);Compared with scar tissue,the expression of TLR4,NF-κB protein and mRNA in scar cancer tissue was significantly increased(P<0.05).The expression of TLR4 and NF-κB in scar cancer tissue was related to the degree of tumor differentiation(P<0.05).After intervention with TLR4 inhibitor TAK-242,the proliferation activity of scar cancer cells was significantly reduced(P<0.05),and the protein expression of TLR4,NF-κB,MMP9,and TGF-β1 was downregulated(P<0.05).Conclusion The TLR4/NF-κB signaling pathway is involved in the pathological process of scar tissue carcinogenesis,and the TLR4 inhibitor TAK-242 can inhibit scar cancer proliferation,which is expected to become a new target for scar tissue treatment.

关 键 词：Toll样受体4 核转录因子ΚB 增生性瘢痕 瘢痕癌 成纤维细胞 

分 类 号：R619.6[医药卫生—外科学]