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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

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文章导航 > 药学实践与服务  > 2016 >  34(3): 219-222,274
姜文丽, 黄才国. Wentilactone A抑制小细胞肺癌系NCI-H1688细胞的迁移研究[J]. 药学实践与服务, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
引用本文: 姜文丽, 黄才国. Wentilactone A抑制小细胞肺癌系NCI-H1688细胞的迁移研究[J]. 药学实践与服务, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
shu
JIANG Wenli, HUANG Caiguo. Wentilactone A inhibition of migration of small cell lung carcinoma NCI-H1688 cell line[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
Citation: JIANG Wenli, HUANG Caiguo. Wentilactone A inhibition of migration of small cell lung carcinoma NCI-H1688 cell line[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
shu

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。
    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.
  • [1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
    [2] Chen W, Zheng R, Zhang S, et al. Report of cancer incidence and mortality in China, 2010[J]. Ann Transl Med, 2014, 2(7):61.
    [3] Ulahannan SV, Brahmer JR. Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer[J]. Cancer Invest, 2011,29(4):325-337.
    [4] Modesto JL, Hull A, Angstadt AY, et al. NNK reduction pathway gene polymorphisms and risk of lung cancer[J]. Mol Carcinog, 2015, 54(Suppl 1):E94-E102.
    [5] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2016,66(1):7-30.
    [6] Stinchcombe TE,Gore EM, Limited-stage small cell lung cancer:current chemoradiotherapy treatment paradigms[J]. Oncologist, 2010,15(2):187-195.
    [7] Johnson BE. Management of small cell lung cancer[J]. Clin Chest Med, 2002,23(1):225-239.
    [8] Traven K, Sinreih M, Stojan J, et al. Ruthenium complexes as inhibitors of the aldo-keto reductases AKR1C1-1C3[J]. Chem Biol Interact, 2015, 234:349-359.
    [9] Stefane B, Brozic P, Vehovc M, et al. New cyclopentane derivatives as inhibitors of steroid metabolizing enzymes AKR1C1 and AKR1C3[J]. Eur J Med Chem, 2009,44(6):2563-2571.
    [10] Penning TM. The aldo-keto reductases (AKRs):Overview[J]. Chem Biol Interact, 2015,234:236-246.
    [11] Rizner TL, Penning TM. Role of aldo-keto reductase family 1(AKR1) enzymes in human steroid metabolism[J]. Steroids, 2014,79:49-63.
    [12] Haddad SA, Lunetta KL, Ruiz-Narváez EA, et al. Hormone-related pathways and risk of breast cancer subtypes in African American women[J]. Breast Cancer Res Treat, 2015,154(1):145-154.
    [13] Naumann JM, Messinger J, Bureik M. Human 20alpha-hydroxysteroid dehydrogenase (AKR1C1)-dependent biotransformation with recombinant fission yeast Schizosaccharomyces pombe[J]. J Biotechnol, 2010,150(1):161-170.
    [14] Byrns MC, Jin Y, Penning TM. Inhibitors of type 517beta-hydroxysteroid dehydrogenase (AKR1C3):overview and structural insights[J]. J Steroid Biochem Mol Biol, 2011,125(1-2):95-104.
    [15] Matsunaga T, Hojo A, Yamane Y, et al. Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers[J]. Chem Biol Interact, 2013,202(1-3):234-242.
    [16] Jaiswal AK. Nrf2 signaling in coordinated activation of antioxidant gene expression[J]. Free Radic Biol Med, 2004,36(10):1199-1207.
    [17] Nishinaka T, Miura T, Okumura M, et al. Regulation of aldo-keto reductase AKR1B10 gene expression:involvement of transcription factor Nrf2[J]. Chem Biol Interact, 2011,191(1-3):185-191.
    [18] Kaspar JW, Niture SK, Jaiswal AK. Nrf2:INrf2(Keap1) signaling in oxidative stress[J]. Free Radic Biol Med, 2009,47(9):1304-1309.
    [19] Cheng X, Ku CH, Siow RC. Regulation of the Nrf2 antioxidant pathway by microRNAs:New players in micromanaging redox homeostasis[J]. Free Radic Biol Med, 2013,64:4-11.
    [20] Brown SL, Sekhar KR, Rachakonda G, et al. Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)-regulated stress pathway[J]. Cancer Res, 2008,68(2):364-368.
    [21] 田鹤,姜文丽,楼国良,等.AKR1C1在非小细胞肺癌的表达及功能分析[J].临床肿瘤学杂志,2015,20(6):487-491.
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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
    • 基金项目:  国家自然科学基金面上项目(41576160,81473239)
  • 收稿日期: 2016-01-27
  • 修回日期: 2016-03-31

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。

English Abstract

姜文丽, 黄才国. Wentilactone A抑制小细胞肺癌系NCI-H1688细胞的迁移研究[J]. 药学实践与服务, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
引用本文: 姜文丽, 黄才国. Wentilactone A抑制小细胞肺癌系NCI-H1688细胞的迁移研究[J]. 药学实践与服务, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
shu
JIANG Wenli, HUANG Caiguo. Wentilactone A inhibition of migration of small cell lung carcinoma NCI-H1688 cell line[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
Citation: JIANG Wenli, HUANG Caiguo. Wentilactone A inhibition of migration of small cell lung carcinoma NCI-H1688 cell line[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(3): 219-222,274. doi: 10.3969/j.issn.1006-0111.2016.03.007
shu

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