侯新垓,刘 长,阮祥信.STAT3小分子化合物LLL-HS-1抑制人肺癌A549细胞增殖的研究[J].肿瘤学杂志,2016,22(7):565-568. |
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 |
投稿时间:2015-07-13 |
DOI:10.11735/j.issn.1671-170X.2016.07.B008 |
|
|
中文关键词: 信号转导与转录因子3 裸鼠 肺肿瘤 LLL-HS-1 |
英文关键词:signal transduction and transcription factor 3 nude mice lung neoplasms LLL-HS-1 |
基金项目:武汉市重点攻关计划(201161038347) |
|
摘要点击次数: 2017 |
全文下载次数: 861 |
中文摘要: |
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(p-STAT3)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)mm3,(487.2±78.6)mm3,明显小于对照组(1989.5±214.3)mm3(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。 |
英文摘要: |
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:low-dose 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 target-specificity. 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)mm3 and (487.2 ± 96.1)mm3 vs (1989.5 ± 234.3)mm3(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 low-dose 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. |
在线阅读
查看全文 查看/发表评论 下载PDF阅读器 |