IGF2BP1在口腔鳞癌细胞耐药中的作用及机制探讨  

Insight into the role of IGF2BP1 in drug resistant mechanism of oral squamous cell carcinoma

作　　者：谢非 秦星[1] 童桐 蒋英英 张建军[1] XIE Fei;QIN Xing;TONG Tong;JIANG Ying-ying;ZHANG Jian-jun(Department of Oromaxillofacial Head and Neck Oncology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,College of Stomatology,Shanghai Jiao Tong University,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai Key Laboratory of Stomatology,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海200011

出　　处：《上海口腔医学》2021年第5期456-461,共6页Shanghai Journal of Stomatology

基　　金：国家自然科学基金(81972573、81772933);上海市科学技术委员会科研计划项目(18JC1413700);上海高水平地方高校创新团队。

摘　　要：目的:探讨IGF2BP1在口腔鳞癌细胞顺铂耐药中的作用和机制。方法:运用小剂量间歇诱导法诱导顺铂敏感的口腔鳞癌细胞HN30,建立顺铂耐药口腔鳞癌细胞系HN30/DDP。通过蛋白免疫印迹方法检测亲本株与耐药株的IGF2BP1表达差异;利用siRNA和慢病毒过表达载体分析IGF2BP1基因表达水平降低或升高对癌细胞顺铂耐药的影响;应用MTT法检测IGF2BP1基因降低或升高后口腔鳞癌细胞对顺铂的IC50。采用SPSS 17.0软件包对数据进行统计学分析。结果:成功建立顺铂耐药的口腔鳞癌细胞系HN30/DDP,耐药细胞株较亲本株的耐药性明显提高。敲低HN30/DDP中的IGF2BP1表达水平,细胞耐药性降低;反之,亲本株细胞过表达IGF2BP1后,细胞耐药性提高。Akt信号通路活化是介导IGF2BP1促进口腔鳞癌细胞顺铂耐药的关键因素。结论:IGF2BP1与口腔鳞癌的顺铂耐药密切相关。IGF2BP1可通过激活下游Akt信号通路,促进口腔鳞癌细胞耐药。PURPOSE:This study focused on the role and mechanism of IGF2 BP1 in cell cisplatin resistance of oral squamous cell carcinoma.METHODS:Low-dose intermittent induction method was used to induce cisplatin-sensitive oral squamous cell carcinoma cell line HN30,and establish cisplatin-resistant cell line HN30/DDP.Western blot was used to detect the protein expression level of IGF2 BP1 in parental and resistant cell line.Knockdown or overexpression of IGF2 BP1 by RNAi and lentivirus transfection method was utilized to analyze the effect of decreased or increased the gene expression of IGF2 BP1 on cisplatin resistance.MTT method was used to detect the change of IC_(50).Statistical analysis of data was performed using SPSS 17.0 software package.RESULTS:Cisplatin-resistant oral squamous cell carcinoma cell line was successfully established.The IC_(50) of the drug-resistant cells was significantly higher than that of the parental cells.Knocking down the expression level of IGF2 BP1 in drug-resistant strains reduced cell resistance;on the contrary,after overexpression of IGF2 BP1 in parental cells dramatically increased cisplatin resistance.Mechanically,activation of Akt signaling pathway was the key factor mediating IGF2 BP1 to promote cisplatin resistance in oral squamous cell carcinoma.CONCLUSIONS:IGF2 BP1 is significantly associated with cisplatin resistance in oral squamous cell carcinoma.IGF2 BP1 can promote cisplatin resistance of oral squamous cells by activating downstream Akt signaling pathway.

关 键 词：口腔鳞癌 IGF2BP1 化疗耐药 顺铂 

分 类 号：R739.8[医药卫生—肿瘤]