Wentilactone A抑制小细胞肺癌系NCI-H1688细胞的迁移研究  

Wentilactone A inhibition of migration of small cell lung carcinoma NCI-H1688 cell line

作　　者：姜文丽[1] 黄才国[1] 

机构地区：[1]第二军医大学基础部生物化学与分子生物学教研室,上海200433

出　　处：《药学实践杂志》2016年第3期219-222,274,共5页Journal of Pharmaceutical Practice

基　　金：国家自然科学基金面上项目(41576160;81473239)

摘　　要：目的探讨小分子化合物Wentilactone A(WA)抑制小细胞肺癌(small cell lung cancer,SCLC)细胞系NCIH1688细胞迁移的机制。方法采用划痕实验、噻唑蓝[3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]实验检测小分子化合物WA对细胞迁移和增殖能力的影响。免疫荧光实验检测化合物WA作用后SCLC细胞系NCI-H1688细胞中ATF3蛋白的表达。Western blot验证ATF3/Nrf2/AKRIC1信号通路的关键蛋白。结果小分子化合物WA抑制SCLC细胞系NCI-H1688细胞的迁移和增殖,加入化合物WA 24 h组与48 h组的IC_(50)分别为(1.03±0.30)和(0.46士0.18)μmol/L。WA作用组NCI-H1688细胞的相对迁移距离为(8.73±1.06)mm,低于对照组的(15.63±3.11)mm,过表达AKR1C1基因后NCI-H1688细胞迁移距离为(24.37±0.90)mm,过表达AKR1C1基因并且WA作用后NCI-H1688细胞的迁移距离为(14.17±1.31)mm,差异有统计学意义(P<0.05)。ATF3是AKR1C1基因的负性调节因子,化合物WA作用后,ATF3蛋白表达水平升高,抑制Nrf2与ARE结合,从而抑制AKR1C1蛋白的表达。结论 WA通过ATF3/Nrf2/AKR1C1信号通路抑制SCLC细胞系NCI-H1688细胞的迁移和增殖。Objective To investigate mechanism of Wentilactone A （WA） inhibition of small cell lung cancer（SCLC） cell line NCI-H1688 migration. Methods The migration and proliferation were analyzed by wounding-healing assay and MTT assay [3- （4,5-Dimethylthiazol-2-yl） -2,5-diphenyltetrazolium bromide, MTT]. Immunofluorescence was used to confirm the ex- pression of ATF3 protein after WA treatment. Western blot was used to examine the expression of key proteins in ATF3/ Nrf2/AKR1C1 signal pathway. Results WA inhibits the proliferation and migration of SCLC. MTT analysis showed WA in- hibits the proliferation of NCI-H1688 cell line in a time-dependent manner. The number of migrated cells in WA treatment group was （8.73±1.06） ram, which was lower than that of control group （15. 63±3.11） mm, The number of migrated cells in AKR1C1 expression group was （24.37±0.90） mm, the number of migrated cells in AKR1C1 expression and WA treatment group was （14.17± 1.31） mm, with significant difference （P〈0.05）. WA enhances the nuclear expression of ATF3, and then reduces the expression of p Nrf2 and AKR1C1. Conclusion WA inhibits the proliferation and migration of SCLC through ATF3/Nrf2/AKR1C1 signal pathway.

关 键 词：Wentilactone A 小细胞肺癌 迁移 增殖 

分 类 号：R965[医药卫生—药理学] R979.1[医药卫生—药学]