Wentilactone A induces cell apoptosis by targeting AKR1C1 gene via the IGF-1R/IRS1/PI3K/AKT/Nrf2/FLIP/Caspase-3 signaling pathway in small cell lung cancer.
Wentilactone A induces cell apoptosis by targeting AKR1C1 gene via the IGF-1R/IRS1/PI3K/AKT/Nrf2/FLIP/Caspase-3 signaling pathway in small cell lung cancer.
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Wentilactone A 通过 IGF-1R/IRS1/PI3K/AKT/Nrf2/FLIP/Caspase-3 信号通路靶向 AKR1C1 基因诱导小细胞肺癌细胞凋亡
DOI：
10.3892/ol.2018.9486
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发表时间：
2018-11
期刊：
影响因子：
2.9
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Jiang W;Meng L;Xu G;Lv C;Wang H;Tian H;Chen R;Jiao B;Wang B;Huang C
Wentilactone A（WA）是一种海洋衍生化合物，可抑制NCI-H446的增殖，如先前的研究所示;然而，WA的抗SCLC机制尚未得到充分研究。本研究旨在探讨WA在体内外抗小细胞肺癌的作用机制。细胞计数试剂盒-8测定细胞生长，流式细胞术分析细胞凋亡，裸鼠移植瘤用于检测WA处理后SCLC的生长。利用生物信息学方法对WA的目的基因进行验证。逆转录-定量聚合酶链反应和蛋白质印迹法用于检查醛酮还原酶家族1成员C1（AKR 1C 1）的mRNA和蛋白质水平，和AKR 1C 1相关蛋白之前和之后WA治疗。分别在用AKR 1C 1敲低或过表达载体转染之前和之后测定细胞生长、凋亡和裸鼠异种移植物的生长。AKR 1C 1是WA的靶基因。AKR 1C 1表达降低和WA治疗通过胰岛素样生长因子-1受体/胰岛素受体底物1/磷酸肌醇3-激酶/AKT/核因子红细胞2相关因子2/Fas相关死亡结构域样白细胞介素-1转化酶样抑制蛋白/Caspase-3途径促进SCLC细胞凋亡。WA通过靶向AKR 1C 1基因抑制SCLC细胞的增殖并诱导其凋亡。WA可能是一种新的AKR 1C 1靶向药物候选人在未来的治疗小细胞肺癌。
Wentilactone A (WA), a marine-derived compound, inhibits proliferation of NCI-H446, as demonstrated by previous research; however, the anti-SCLC mechanism underlying WA was not fully investigated. The present study aimed to investigate the anti-SCLC mechanism underlying WA in vitro and in vivo. Cell Counting Kit-8 was used to assay cell growth, flow cytometry was conducted to analyze cell apoptosis and nude mice xenografts were used to examine SCLC growth following WA treatment. Bioinformatics was used for verification of the target gene of WA. Reverse transcription-quantitative polymerase chain reaction and western blot were used to examine aldo-keto reductase family 1 member C1 (AKR1C1) mRNA and protein levels, and AKR1C1-associated proteins prior to and following WA treatment. Cell growth, apoptosis and growth of nude mice xenografts were assayed prior to and following transfection with AKR1C1 knockdown or overexpression carriers, respectively. It was determined that AKR1C1 was a target gene of WA. Decreased AKR1C1 expression and WA treatment promoted apoptosis in SCLC via the insulin like growth factor-1 receptor/insulin receptor substrate 1/phosphoinositide 3-kinase/AKT/nuclear factor-erythroid 2-associated factor 2/Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein/Caspase-3 pathway. WA attenuated the proliferation and induced the apoptosis of SCLC cells in vitro and in vivo by targeting the AKR1C1 gene. WA may be a novel AKR1C1-targeted drug candidate for the treatment of SCLC in the future.
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影响因子：
3.7
作者：
Ge QM;Huang CM;Zhu XY;Bian F;Pan SM
通讯作者：
Pan SM
影响因子：
11.5
作者：
Homma, Shinsuke;Ishii, Yukio;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki
影响因子：
5.7
作者：
Wang, Xia;Chen, Wenshu;Lin, Yong
通讯作者：
Lin, Yong
DOI：
10.2147/lctt.s90694
发表时间：
2016
期刊：
Lung Cancer (Auckland, N.Z.)
影响因子：
--
作者：
Tian H;Li X;Jiang W;Lv C;Sun W;Huang C;Chen R
通讯作者：
Chen R
NRF2：氧化应激中的INRF2（KEAP1）信号传导。
影响因子：
7.4
作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
通讯作者：
Jaiswal, Anil K.