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

姜文丽; 黄才国

doi:10.3969/j.issn.1006-0111.2016.03.007

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

doi: 10.3969/j.issn.1006-0111.2016.03.007

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

基金项目: 国家自然科学基金面上项目(41576160,81473239)

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

Department of Biochemistry and Molecular Biology, Faculty of Basic Medicine, Second Military Medical University, Shanghai 200433, China

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NCI-H1688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/AKR1C1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IC₅₀分别为(1.03±0.30)和(0.46±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。
- WentilactoneA /
- 小细胞肺癌 /
- 迁移 /
- 增殖
Abstract: 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 expression 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 inhibits 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) mm, 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.
- Wentilactone A /
- SCLC /
- migration /
- proliferation

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

doi: 10.3969/j.issn.1006-0111.2016.03.007

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

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

doi: 10.3969/j.issn.1006-0111.2016.03.007

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

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

Department of Biochemistry and Molecular Biology, Faculty of Basic Medicine, Second Military Medical University, Shanghai 200433, China

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

doi: 10.3969/j.issn.1006-0111.2016.03.007

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

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

doi: 10.3969/j.issn.1006-0111.2016.03.007

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

English Abstract

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

Department of Biochemistry and Molecular Biology, Faculty of Basic Medicine, Second Military Medical University, Shanghai 200433, China

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