【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。更多还原

【Abstract】 [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.更多还原