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首页> 外文期刊>Cancer prevention research. >Fluvastatin Inhibits HMG-CoA Reductase and Prevents Non-Small Cell Lung Carcinogenesis
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Fluvastatin Inhibits HMG-CoA Reductase and Prevents Non-Small Cell Lung Carcinogenesis

机译：氟伐他汀抑制HMG-COA还原酶并防止非小细胞肺癌发生

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摘要

Lung cancer is the leading cause of cancer-related death worldwide. However, promising agents for lung cancer prevention are still very limited. Identification of preventive targets and novel effective preventive agents is urgently needed for clinical applications. In this study, we found that fluvastatin targeted 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR), which a rate-limiting enzyme in the mevalonate pathway, and inhibited non-small cell lung cancer (NSCLC) tumorigenesis. Initially, we demonstrated that HMGCR is overexpressed in human lung adenocarcinoma tissues compared with normal tissues. Knockdown of HMGCR in NSCLC cells attenuated growth and induced apoptosis in vitro and in vivo. Furthermore, we found that fluvastatin, an inhibitor of HMGCR, suppressed NSCLC cell growth and induced apoptosis. Intriguingly, fluvastastin functions by inhibiting the HMGCR-driven Braf/MEK/ERK1/2 and Akt signaling pathways. Notably, fluvastatin attenuated tumor growth in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis and in a patient-derived xenograft lung tumor model. Overall, our findings suggest that fluvastatin might be promising chemopreventive or potential therapeutic drug against NSCLC tumorigenesis, providing hope for rapid clinical translation.
机译：肺癌是全世界癌症相关死亡的主要原因。然而，肺癌预防的有前途的药剂仍然非常有限。迫切需要鉴定预防靶标和新型有效预防剂的临床应用。在这项研究中，我们发现氟伐他汀靶向3-羟基-3-甲基戊族辅酶A（HMG-COA）还原酶（HMGCR），其在甲羟戊酯途径中是限流酶，并抑制非小细胞肺癌（NSCLC）肿瘤发生。最初，我们证明，与正常组织相比，HMGCR在人肺腺癌组织中过表达。 NSCLC细胞中HMGCR的敲低衰减生长和体内诱导细胞凋亡。此外，我们发现氟伐他汀，HMGCR的抑制剂，抑制NSCLC细胞生长和诱导的细胞凋亡。有趣的，通过抑制HMGCR驱动的BRAF / MEK / ERK1 / 2和AKT信号传导途径来起作用。值得注意的是，氟伐他汀在4-（甲基亚氨基氨基氨基氨基氨基氨基）-1-（3-吡啶基）-1-丁酮（NNK）诱导的肺肿瘤内酯和患者衍生的异种移植肺肿瘤模型中肿瘤生长。总体而言，我们的研究结果表明，氟伐他汀可能对NSCLC肿瘤发生的潜在治疗药物有望，为快速临床翻译提供希望。

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  • 来源
    《Cancer prevention research.》 |2019年第12期|共12页
  • 作者

    Zhang Tianshun; Bai Ruihua; Wang Qiushi; Wang Keke; Li Xiang; Liu Kangdong; Ryu Joohyun; Wang Ting; Chang Xiaoyu; Ma Weiya; Bode Ann M.; Xia Qingxin; Song Yongping; Dong Zigang;

  • 作者单位

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    China US Henan Hormel Canc Inst Zhengzhou Henan Peoples R China;

    China US Henan Hormel Canc Inst Zhengzhou Henan Peoples R China;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

    Zhengzhou Univ Affiliated Canc Hosp Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Affiliated Canc Hosp Zhengzhou Henan Peoples R China;

    Univ Minnesota Hormel Inst 801 16th Ave NE Austin MN 55912 USA;

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  • 正文语种 eng
  • 中图分类 肿瘤学;
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