Tiam1基因沉默增加紫杉醇抑制头颈部鳞状细胞系SCC Ⅶ的机制  

Tiam1 gene silencing increase anti-cancer efficacy of paclitaxel on head and neck squamous cell carcinoma SCC Ⅶ

作　　者：肖平[1] 万仁强[1] 李泽泳[2] 林勇 傅向军[1] XIAO Ping;WAN Ren - qiang;LI Ze - yong;LIN Yong;FU Xiang - jun(Department of Otolaryngology - Head and Neck Surgery,the Second People's Hospital of Guangdong Province,Guangzhou 510317,Guangdong,China)

机构地区：[1]广东省第二人民医院耳鼻咽喉头颈外科,广东广州510317 [2]广东省第二人民医院生物实验中心,广东广州510317 [3]喀什地区第一人民医院耳鼻咽喉科,新疆喀什844000

出　　处：《广东医学》2019年第10期1367-1371,共5页Guangdong Medical Journal

基　　金：广东省医学科研基金资助项目(编号:A2016324)

摘　　要：目的构建Tiam1 RNA干扰载体,转染并观测Tiam1基因沉默效果,探索基于Tiam1基因沉默的影响下,紫杉醇对头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)治疗的敏感性及其抗癌机制。方法构建Tiam1 RNA干扰载体,体外培养头颈部鳞状细胞癌小鼠HNSCC细胞株SCCⅦ细胞,G418抗性验证Tiam1 RNAi的效果,利用RT-qPCR、Western blot法探索Tiam1基因沉默后紫杉醇对SCCⅦ细胞的表皮生长因子受体(EGFR)、Rac1基因和蛋白的表达。结果成功构建Tiam1 RNA干扰载体,并转染入SCCⅦ细胞,利用G418证实Tiam1 RNAi质粒可明显抑制Tiam1的表达,造成Tiam1基因沉默。紫杉醇给药后,HNSCC细胞侵袭和迁移能力降低,结合Tiam1基因沉默后,EGFR、Rac1表达也减弱,差异有统计学意义(P<0.05)。由此推测紫杉醇可以通过Tiam1/Rac1、Tiam1/EGFR信号途径起抑癌作用。结论体外实验证实Tiam1基因沉默后,紫杉醇可抑制HNSCC的侵袭与迁移能力,使得EGFR和Rac1的表达降低,推测紫杉醇可能通过减弱Rac1的表达来削弱肿瘤的敏感性,阻碍HNSCC细胞株SCCⅦ细胞新生,抑制其转移,Tiam1基因沉默使紫杉醇抑癌的作用大大提高。Objective To construct the Tiam1 RNA interference vector, with which to observe its silencing effect. Based on the influence of Tiam1 gene silencing, to investigate the mechanism and sensitivity of paclitaxel on head and neck squamous cell carcinoma(HNSCC). Methods Tiam1 RNA interference vector was constructed. The cervical squamous cell carcinoma HNSCC cell line SCC Ⅶ cells were cultured in vitro. G418 resistance was used to verify the effect of Tiam1 RNAi. RT-qPCR and Western blot were used to explore the expression of EGFR and Rac1 paclitaxel-induced HNSCC cell line SCC Ⅶ after silence of Tiam1 gene. Results The Tiam1 RNA interference vector was successfully constructed and transfected into SCC Ⅶ cells. It was confirmed by G418 that Tiam1 RNAi plasmid significantly inhibited the expression of Tiam1. After paclitaxel administration, the invasion and migration capacities of HNSCC cells were reduced. After silencing of Tiam1 gene, the expression of EGFR and Rac1 was significantly down-regulated(P<0.05). Conclusion In vitro experiments confirms that paclitaxel can inhibit the invasion and migration of HNSCC, and reduce the expression of EGFR and Rac1. It is speculated that paclitaxel may weaken the sensitivity of tumor by attenuating the expression of Rac1, hinder the regeneration of HNSCC cell line SCC Ⅶ, inhibit the metastasis. Tiam1 gene silencing greatly enhances the anti-cancer effect of paclitaxel.

关 键 词：TIAM1基因 紫杉醇 头颈部鳞状细胞癌 

分 类 号：R739.81[医药卫生—肿瘤] R979.1[医药卫生—临床医学]