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目的:研究Toll样受体4(TOLL-like receptor 4,TLR4)分子高表达与口腔鳞状细胞癌预后的关系,探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)通过TLR4信号通路间接调控口腔鳞状细胞癌增殖转移的潜在机制。方法:采用免疫组织化学法检测50例口腔鳞状细胞癌患者病理切片中TLR4的表达;使用m TOR抑制剂(雷帕霉素)作用于口腔鳞状细胞癌细胞系CAL27后,再用LPS激活TLR4信号通路,通过MTT法检测CAL27细胞的增殖能力,Transwell法检测CAL27细胞的迁移能力,Western免疫印迹检测其对肿瘤细胞中NF-κB及MAPK信号通路的影响。采用SPSS 16.0软件包对数据进行统计学分析。结果:TLR4分子高表达与口腔鳞状细胞癌预后差显著相关(P<0.05);雷帕霉素能够显著抑制TLR4激活后的CAL27细胞的增殖和迁移能力(P<0.01),显著抑制TLR4下游的NF-κB及MAPK信号通路(P<0.01)。结论:m TOR通过TLR4信号通路调控口腔鳞状细胞癌的增殖与转移,有望成为治疗口腔鳞状细胞癌的新靶点。
OBJECTIVE: To study the relationship between the high expression of Toll-like receptor 4 (TLR4) and the prognosis of oral squamous cell carcinoma (OSCC), and to investigate the relationship between mammalian target of rapamycin (mTOR) and TLR4 Signal Pathway Regulates Potential Mechanism of Proliferation and Metastasis in Oral Squamous Cell. Methods: Immunohistochemical method was used to detect the expression of TLR4 in pathological sections of 50 patients with oral squamous cell carcinoma. After oral administration of mTOR inhibitor (rapamycin) to oral squamous cell carcinoma cell line CAL27, LPS was activated TLR4 signaling pathway. The proliferation of CAL27 cells was detected by MTT assay. The migration ability of CAL27 cells was detected by Transwell assay. The effect of NF-κB and MAPK signal transduction pathway in tumor cells was detected by Western blotting. Data were analyzed statistically using SPSS 16.0 software package. Results: The high expression of TLR4 was significantly associated with the poor prognosis of oral squamous cell carcinoma (P <0.05). Rapamycin could significantly inhibit the proliferation and migration of CAL27 cells after TLR4 activation (P <0.01) and significantly inhibit the downstream of TLR4 NF-κB and MAPK signaling pathways (P <0.01). Conclusion: m TOR regulates the proliferation and metastasis of oral squamous cell carcinoma through TLR4 signaling pathway, which is expected to become a new target for the treatment of oral squamous cell carcinoma.