TGF-βRⅡ和NF-κB在口腔鳞状细胞癌的表达及临床意义

上海口腔医学 ›› 2016, Vol. 25 ›› Issue (6): 729-733.

TGF-βRⅡ和NF-κB在口腔鳞状细胞癌的表达及临床意义

蒋丽兰, 赵娅军, 李勇

重庆医科大学附属口腔医院口腔颌面外科,口腔疾病与生物医学重庆市重点实验室, 重庆市高校市级口腔生物医学工程重点实验室,重庆 401147

收稿日期:2016-06-13 出版日期:2016-12-25 发布日期:2016-12-29
通讯作者: 李勇,E-mail:1243636810@qq.com
作者简介:蒋丽兰（1990-）,女,硕士,E-mail: 953119965@qq.com

Expressions and clinical significance of TGF-βRⅡ and NF-κB in oral squamous cell carcinoma

JIANG Li-Lan, ZHAO Ya-Jun, LI Yong

Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Stomatology, Chongqing Medical University; Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education. Chongqing 401147, China

Received:2016-06-13 Online:2016-12-25 Published:2016-12-29

摘要/Abstract

摘要： 目的检测核因子κappa-B(Nuclear Factor κappa-B,NF-κB)和转化生长因子βⅡ型受体(transforming growth factor β receptorⅡ,TGF-βRⅡ)在口腔鳞状细胞癌中的表达,探讨两者与口腔鳞癌之间的关系及意义。方法收集2010年7月—2011年7月在治疗的60例OSCC患者信息,应用免疫组织化学方法,检测60例口腔鳞癌组织、20例癌旁组织、29例转移淋巴结组织和10例炎性淋巴结组织中NF-κB和TGF-βRⅡ的表达。采用SPSS20.0软件包对数据进行统计学分析。结果NF-κB在口腔鳞癌原发灶和转移淋巴结中的表达显著高于癌旁正常组织和炎性淋巴结组织（P<0.05）。TGF-βRⅡ在口腔鳞癌原发灶和转移淋巴结中表达显著低于癌旁正常组织和炎性淋巴结组织(P<0.05)。NF-κB和TGF-βRⅡ呈负相关关系(P<0.05)。分化程度低、病理分级高和有淋巴结转移的口腔鳞癌患者,NF-κB显著高于分化程度高、病理分级低和无淋巴结转移者（P<0.05）。NF-κB与口腔鳞癌患者的预后相关(P<0.05)。结论NF-κB和TGF-βRⅡ呈负相关关系,与口腔鳞癌的发生、发展和转移有关;NF-κB与患者预后相关;NF-κB可能通过下调TGF-βRⅡ的表达,促进血管生成而促进肿瘤的生长和转移。

关键词: 口腔鳞状细胞癌, NF-κ, B, TGF-β, RⅡ, 肿瘤转移

Abstract: PURPOSE: To investigate the expression of nuclear factor κappa-B (NF-κB) and transforming growth factor β receptor Ⅱ (TGF-βRⅡ) and their clinical pathological significance in oral squamous cell carcinoma(OSCC). METHODS: The expression of NF-κB and TGF-βRⅡ in 60 OSCC samples, 20 adjacent tissues, 29 metastatic lymph nodes and 10 non-metastatic lymph nodes were detected by immunohistological method. Statistical analysis was performed with SPSS 20.0 software package. RESULTS: The expression of NF-κB in OSCC and metastatic lymph nodes was significantly higher than that in the adjacent tissues and non-metastatic lymph nodes, respectively (P<0.05). However, the expression of TGF-βRⅡ in OSCC and metastatic lymph nodes was significantly lower than that in the adjacent tissues and non-metastatic lymph nodes, respectively (P<0.05). NF-κB was negatively correlated with TGF-βRⅡ. The expression of NF-κB in patients with lower differentiation, lymphatic metastasis and higher grade were significantly higher than in patients with higher differentiation, lower grade and without lymphatic metastasis (P<0.05), respectively. NF-κB was a predicator of OSCC. CONCLUSIONS: NF-κB is negatively correlated with TGF-βRⅡ.NF-κB and TGF-βRⅡ are associated with the progression of OSCC. NF-κB may promote angiogenesis through down-regulating the expression of TGF-βRⅡ, which promotes progression of OSCC.

Key words: Oral squamous cell carcinoma, NF-κ, B, TGF-β, RⅡ, Tumor metastasis

中图分类号:

R739.8

蒋丽兰, 赵娅军, 李勇. TGF-βRⅡ和NF-κB在口腔鳞状细胞癌的表达及临床意义[J]. 上海口腔医学, 2016, 25(6): 729-733.

JIANG Li-Lan, ZHAO Ya-Jun, LI Yong. Expressions and clinical significance of TGF-βRⅡ and NF-κB in oral squamous cell carcinoma[J]. Shanghai Journal of Stomatology, 2016, 25(6): 729-733.

参考文献

[1] Tomikoshi Y, Nomura M, Okudaira N, et al. Enhancement of cytotoxicity of three apoptosis-inducing agents against human oral squamous cell carcinoma cell line by benzoxazinotropone [J]. In Vivo, 2016, 30(5): 645-650.
[2] Park S, Jang WJ, Jeong CH. Nano-biomechanical validation of epithelial-mesenchymal transition in oral squamous cell carcinomas[J]. Biol Pharm Bull, 2016, 39(9): 1488-1495.
[3] Fukumoto I, Koshizuka K, Hanazawa T, et al. The tumor-
suppressive microRNA-23b/27b cluster regulates the MET oncogene in oral squamous cell carcinoma [J]. Int J Oncol, 2016, 49(3): 1119-1129.
[4] Mao Z, Ma X, Rong Y, et al. Connective tissue growth factor enhances the migration of gastric cancer through downregulation of E-cadherin via the NF-κB pathway[J]. Cancer Sci, 2011, 102(1): 104-110.
[5] Wu D, Wu P, Zhang L, et al. NF-κB expression and outcomes in solid tumors: a systematic review and meta-analysis [J]. Medicine (Baitimore), 2015, 94(40): e1687.
[6] Wenxia Meng, Qingjie Xia, Lanyan Wu,et al. Downregulation of TGF-beta receptor types Ⅱ and Ⅲ in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts[J].BMC Cancer,2011.11(88):1-13.
[7] 陆斌, 周永宁, 李强, 等. 胃癌组织TGF-βRⅡ、Smad4、Smad7的表达及其与临床病理特征和生存的关系 [J]. 癌症, 2009, 28(5): 538-542.
[8] Shengwei H, Wenguang X, Zhiyong W, et al. Crosstalk between the HIF-1 and toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment [J]. Oncotarget, 2016,7(25):37773-37789.
[9] Park SJ, Choi YS, Lee S, et al. BIX02189 inhibits TGF-β1-induced lung cancer cell metastasis by directly targeting TGF-β type I receptor [J]. Cancer Lett, 2016, 381(2): 314-322.
[10] Park NR, Cha JH, Jang JW, et al. Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells [J]. Biochem Biophys Res Commun, 2016, 477(4): 568-574.
[11] Hara T, Yoshida E, Shinkai Y, et al. Biglycan intensifies ALK5-Smad2/3 signaling by TGF-β1 and downregulates syndecan-4 in cultured vascular endothelial cells [J]. J Cell Biochem, 2016 Sep 1.
[12] Yoshimoto T, Fujita T, Kajiya M, et al. Aggregatibacter actinomycetemcomitans outer membrane protein 29 (Omp29) induces TGF-β-regulated apoptosis signal in human gingival epithelial cells via fibronectin/integrinβ1/FAK cascade [J].Cell Microbiol, 2016 Apr 28.
[13] Wang L, Zeng H, Wang Q, et al. MED12 methylation by CARM1 sensitizes human breast cancer cells to chemotherapy drugs [J]. Sci Adv, 2015, 1(9): e1500463.
[14] Cheng CM, Shiah SG, Huang CC, et al. Up-regulation of miR-455-5p by the TGF-β-SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B [J]. J Pathol, 2016, 240(1): 38-49.
[15] Kimura I, Kitahara H, Ooi K, et al. Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition [J]. Oncol Lett, 2016, 11(1): 201-207.
[16] Liu X, Yu M, Chen Y, et al. Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats [J]. Braz J Med Biol Res, 2016, 49(9): e5388.
[17] Piva MR, DE Souza LB, Martins-Filho PR, et al. Role of inflammation in oral carcinogenesis (Part Ⅱ): CD8, FOXP3, TNF-α, TGF-β and NF-κB expression [J]. Oncol Lett, 2013, 5(6): 1909-1914.