组织工程与重建外科杂志 ›› 2025, Vol. 21 ›› Issue (1): 14-.

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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

  

  • 出版日期:2025-02-25 发布日期:2025-03-06

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

  • Online:2025-02-25 Published:2025-03-06

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。

关键词:

Abstract:

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.

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