STAT3小分子化合物LLL-HS-1抑制人肺癌A549细胞增殖的研究  

Study on the Inhibition of Small Molecule Compound of STAT3 LLL-HS-1 on Proliferation of Human Lung Cancer Cells A549

作　　者：侯新垓[1] 刘长[1] 阮祥信 李永蓉 徐姗[2] 宋丹丹[2] 李媛媛[2] 聂艳丽[3] 

机构地区：[1]三峡大学第三临床学院,葛洲坝中心医院,湖北宜昌443000 [2]华中师范大学化学学院,湖北武汉430079 [3]湖北省肿瘤医院,湖北武汉430079

出　　处：《肿瘤学杂志》2016年第7期565-568,共4页Journal of Chinese Oncology

基　　金：武汉市重点攻关计划(201161038347)

摘　　要：[目的]探讨信号转导与转录因子3(STAT3)在肺癌细胞中的表达,并观察以其为靶点的化合物LLL-HS-1腹腔给药对肿瘤的抑制作用。[方法]皮下接种A549细胞成瘤1周后,15只小鼠随机3组,以低剂量(10mg/kg)和高剂量(20mg/kg)LLL-HS-1腹腔给药,对照组接受安慰剂。采用Western blot检测肺癌A549细胞蛋白中STAT3的表达及其磷酸化STAT3(pSTAT3)状态。最终以肿瘤体积大小为衡量药效学的指标。[结果 ]体外研究发现,化合物LLL-HS-1可以抑制STAT3酪氨酸残基705磷酸化,而且具有靶点特异性。持续3周给药,发现高和低剂量组对肿瘤的增长有明显的抑制效果,平均肿瘤体积分别为(336.8±60.5)mm^3,(487.2±78.6)mm^3,明显小于对照组(1989.5±214.3)mm^3(F=33.8,P=0.0001;F=17.4,P=0.005)。对照组瘤重明显高于高和低剂量组,各组间比较,F=9.2,P=0.02。[结论]化合物LLL-HS-1对肺腺癌细胞有明显抑制作用,可能通过下调STAT3的磷酸化,诱导肿瘤细胞凋亡来实现。[Objective] To investigate the expression of the signal transduction and transcription factor 3（STAT3） in lung cancer cells,and to study the inhibition of LLL-HS-1 intraperitoneal administertion targeting on STAT3 on proliferation of tumor. [Methods] After one week of subcutaneous inoculation of A549 cells in mice,15 mice were randomly divided into three groups：lowdose group（10mg/kg）,high-dose group（20mg/kg）,and control group（placebo）. Protein expression of STAT3 and phosphorylated STAT3（p-STAT3） state were detected by Western blot method. Tumor volume was analyzed as final pharmacodynamic indicator. [Results] The study in vitro indicated that LLL-HS-1 inhibited phosphorylation of STAT3 tyrosine residue 705 with a targetspecificity. After three weeks administration,LLL-HS-1 significantly inhibited tumor growth. Average volumes in high- and low-dose groups were significantly less than those in the control group[（336.8 ± 84.5）mm^3 and（487.2 ± 96.1）mm^3 vs（1989.5 ± 234.3）mm^3（F=33.8,P=0.0001;F=17.4,P=0.005）]. Tumor＇s weight in control group was significantly higher than that in high- and lowdose group（F=9.2,P=0.02）. [Conclusion] LLL-HS-1 might significantly inhibit lung adenocarcinoma cells,which is possibly through down-regulation of STAT3 phosphorylation,and inducement of apoptosis in cancer cells.

关 键 词：信号转导与转录因子3 裸鼠 肺肿瘤 LLL-HS-1 

分 类 号：R734.2[医药卫生—肿瘤]