mTOR调控口腔鳞状细胞癌增殖转移的机制研究

doi:10.19438/j.cjoms.2017.05.004

中国口腔颌面外科杂志 ›› 2017, Vol. 15 ›› Issue (5): 397-401.doi: 10.19438/j.cjoms.2017.05.004

mTOR调控口腔鳞状细胞癌增殖转移的机制研究

鞠侯雨，张黎明，任国欣

上海交通大学医学院附属第九人民医院·口腔医学院口腔颌面-头颈肿瘤科，上海市口腔医学重点实验室，上海 200011

收稿日期:2017-03-01 出版日期:2017-08-30 发布日期:2017-10-27
通讯作者: 任国欣，E-mail:renguoxincn@hotmail.com
作者简介:鞠侯雨（1990-），男，硕士，E-mail:juhouyu@sina.com
基金资助:
上海市自然科学基金（14DZ1941402）

Mechanism of mTOR regulating proliferation and metastasis of oral squamous cell carcinoma JV

Hou-yu, ZHANG Li-ming, REN Guo-xin.

Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine;
Shanghai Key Laboratory of Stomatology. Shanghai 200011, China

Received:2017-03-01 Online:2017-08-30 Published:2017-10-27

摘要/Abstract

摘要： 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，mTOR）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mTOR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： mTOR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。

关键词: Toll样受体4, TLR4, mTOR, 口腔鳞状细胞癌, 增殖, 转移

Abstract: PURPOSE: To investigate the correlation of increased expression of TLR4 with poor prognosis in patients with oral squamous cell carcinoma (OSCC), and discuss the potential mechanism of mTOR regulating proliferation and metastasis of OSCC through TLR4 signaling pathway. METHODS: Immunohistochemistry was used to detect the expression of TLR4 in the pathological sections of 50 patients with OSCC. OSCC cell lines CAL27 was pre-treated with inhibitor of mTOR (rapamycin), then stimulated with lipopolysaccharide (LPS), a TLR4 ligand. MTT was used to detect cell proliferation and transwell assay was used to detect migration of CAL27 cells. Western blot was performed to detect changes in NF-κB and MARK signaling pathway. The data were analyzed using SPSS 16.0 software package. RESULTS: Increased expression of TLR4 showed a significant correlation with poor prognosis in patients with OSCC (P<0.05). Rapamycin could inhibit cell proliferation and migration of CAL27 cells significantly after TLR4 was activated (P<0.01) .Rapamycin suppressed NF-κB and MARK signaling pathway through inhibiting TLR4 signaling pathway. CONCLUSIONS: mTOR can regulate the proliferation and metastasis of OSCC through TLR4 signaling pathway, TLR4 might be a new target for treatment of OSCC.

Key words: Toll like receptor-4, TLR4, mTOR, Oral squamous cell carcinoma, Proliferation, Metastasis

中图分类号:

R739.8

鞠侯雨，张黎明，任国欣. mTOR调控口腔鳞状细胞癌增殖转移的机制研究[J]. 中国口腔颌面外科杂志, 2017, 15(5): 397-401.

Hou-yu, ZHANG Li-ming, REN Guo-xin.. Mechanism of mTOR regulating proliferation and metastasis of oral squamous cell carcinoma JV[J]. China J Oral Maxillofac Surg, 2017, 15(5): 397-401.

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mTOR调控口腔鳞状细胞癌增殖转移的机制研究

Mechanism of mTOR regulating proliferation and metastasis of oral squamous cell carcinoma JV

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