IL-6/JAK2/STAT3对口腔鳞状细胞癌生物学行为的影响  

Influences of IL-6/JAK2/STAT3 on the biological behavior of oral squamous cell carcinoma

作　　者：仝向娟[1] 周晓 钟慧[3] 彭子文 单振锋 TONG Xiangjuan;ZHOU Xiao;ZHONG Hui;PENG Ziwen;SHAN Zhenfeng(Department of Stomatology,Third Xiangya Hospital,Central South University,Changsha 410013,China;Department of Head and Neck Surgery,Hunan Cancer Hospital/Affiliated Cancer Hospital,Xiangya Medical College,Central South University,Changsha 410013,China;School of Life Sciences,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅三医院口腔科,湖南长沙410013 [2]湖南省肿瘤医院中南大学湘雅医学院附属肿瘤医院头颈外科,湖南长沙410013 [3]中南大学生命科学学院,湖南长沙410013

出　　处：《中国耳鼻咽喉颅底外科杂志》2022年第1期89-97,共9页Chinese Journal of Otorhinolaryngology-skull Base Surgery

基　　金：湖南省自然科学基金(2019JJ40216)。

摘　　要：目的观察白细胞介素6抗体(IL-6)/蛋白酪氨酸激酶2抗体(JAK2)/信号传导和转录激活因子3抗体(STAT3)对口腔鳞状细胞癌(简称口腔鳞癌)细胞生物学行为的影响。方法对口腔鳞癌细胞系进行慢病毒转染敲低IL-6基因,设立两组对照,一组为未干预组,另一组为空白载体组。通过CCK8实验和克隆形成实验检测IL-6对口腔鳞癌细胞增殖情况的影响,通过流式细胞术检测细胞周期变化,通过Transwell实验检测IL-6对口腔鳞癌细胞侵袭和迁移能力的影响。利用实时荧光定量PCR以及Western blot方法检测口腔鳞癌细胞中IL-6基因表达下调后其下游通路基因p-STAT3、p-JAK2与肿瘤血管新生有关的蛋白VEGFA、细胞周期调控蛋白Cyclin B1、细胞基质沉积相关蛋白MMP2、细胞凋亡抑制蛋白Survivin、上皮向间质转化相关蛋白Snail和E-Cadherin的表达情况。结果敲低IL-6的口腔鳞癌细胞与对照组细胞比较,增殖率受到明显抑制,差异具有统计学意义(F=13.06,P=0.006);敲低IL-6的口腔鳞癌细胞中G1期细胞百分比下降,G2期细胞百分比上升,差异具有统计学意义(F=5.53,P<0.05);敲低IL-6的口腔鳞癌细胞与对照细胞比较,侵袭能力和迁移能力明显下降,差异具有统计学意义(F=23.59/53.11,P<0.01);口腔鳞癌细胞IL-6表达下调后,JAK2、STAT3、VEGFA、Cyclin B1、MMP2、Snail表达随之明显下降,而E-Cadherin表达显著增加,差异具有统计学意义(P均<0.05)。结论IL-6基因敲低后可明显抑制口腔鳞癌细胞的生长与增殖能力,可能诱导细胞G2期阻滞;抑制STAT3、JAK2、VEGFA、Cyclin B1、MMP2、Snail和Survivin表达,促进E-Cadherin蛋白表达。Objective To investigate the effects of IL-6/JAK2/STAT3 on the biological behavior of oral squamous cancer cells.Methods The oral squamous cell carcinoma cell line was transfected with lentivirus,and the IL-6 gene was knocked down.Two control groups(no intervention group and blank vector group)were set up.The effect of IL-6 on the proliferation of oral squamous cell carcinoma cells was detected by CCK8 experiment and clonal formation experiment,the cellular cycle change was detected by flow cytometry,and the influences of IL-6 on invasion and migration ability of oral squamous cell carcinoma cells were detected by Transwell experiment.Then real-time fluorescence quantitative PCR and Western blot were used to detect the expressions of the downstream channel gene STAT3,JAK2,protein VEGFA related to tumor angiogenesis,cell cycle regulatory protein Cyclin B1,cell matrix deposition-related protein MMP2,apoptosis suppressor protein Survivin,and protein Snail and E-Cadherin related to epithelial-to-interstitial transformation in oral squamous cell carcinoma cells after downregulation of IL-6 gene expression.Results Compared with the control group,the oral squamous cell carcinoma cells with knockout IL-6 were significantly inhibited in proliferation rate,and the difference was statistically significant(P<0.05).The percentage of G1-phase cells in oral squamous cell carcinoma cells with knockout IL-6 decreased significantly while that of G2-phase cells increased significantly,and the differences were statistically significant(both P<0.05).The invasive ability and migration ability of oral squamous cell carcinoma cells with knockout IL-6 decreased significantly compared with the control cells,and the difference was statistically significant(P<0.05).Compared with the control group,the expressions of STAT3,JAK2,VEGFA,Cyclin B1,MMP2,Snail and Survivin protein decreased significantly while E-Cadherin protein expression increased apparently in oral squamous cell carcinoma cells with knockout IL-6(all P<0.05).Conclusion IL-6/JAK2

关 键 词：口腔鳞状细胞癌 白细胞介素6 蛋白酪氨酸激酶2 信号传导和转录激活因子3 细胞增殖 

分 类 号：R739.85[医药卫生—肿瘤]