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首页> 外文期刊>RSC Advances >Long non- coding RNA GACAT1 alleviates doxorubicin and vincristine resistance through a PTEN/ AKT/ mTOR/ S6K1 regulatory pathway in gastric cancer
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Long non- coding RNA GACAT1 alleviates doxorubicin and vincristine resistance through a PTEN/ AKT/ mTOR/ S6K1 regulatory pathway in gastric cancer

机译：长期非编码RNA GACAT1通过PTEN / AKT / MTOR / S6K1调节途径缓解了多柔比星和血管素抗性，胃癌

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摘要

Gastric cancer (GC) is a major global health problem. Chemotherapy is a common therapeutic strategy for cancers including GC. However, chemoresistance strikingly limits the clinical applications of chemotherapeutic drugs. Long non-coding RNAs (lncRNAs) have been widely reported to be implicated in the pathogenesis and chemoresistance of cancers including GC. Our work aims to investigate the roles and molecular mechanisms of lncRNA gastric cancer-associated transcript 1 (GACAT1) in regulating doxorubicin (ADR) and vincristine (VCR) resistance in GC. In this text, RT-qPCR assay showed that GACAT1 expression was markedly reduced in ADR- or VCR-resistant GC (SGC7901/ADR or SGC7901/VCR) cells and GC tissues. CCK-8 assay and flow cytometry analysis revealed that GACAT1 overexpression alleviated the resistance of GC cells to ADR and VCR. RT-qPCR and western blot assay disclosed that GACAT1 deactivated the AKT/mTOR/S6K1 signaling pathway and promoted PTEN expression in SGC7901/ADR or SGC7901/VCR cells. Restoration experiments demonstrated that GACAT1 attenuated ADR or VCR resistance by regulating the PTEN/AKT/mTOR/S6K1 pathway in SGC7901/ADR or SGC7901/VCR cells. In vivo experiments demonstrated that GACAT1 overexpression inhibited tumor growth and enhanced ADR- or VCR-mediated anti-tumor effects in GC xenograft tumor models. Taken together, these data revealed that GACAT1 weakened the resistance of GC cells to ADR and VCR by the PTEN/AKT/mTOR/S6K1 regulatory pathway in vitro and in vivo, shedding new light on GACAT1 upregulation as a potential strategy to alleviate chemoresistance in GC.
机译：胃癌（GC）是一个主要的全球健康问题。化疗是一种常见的癌症治疗策略，包括GC。然而，化学抑制令人惊讶地限制了化学治疗药物的临床应用。已经普遍据报道，长期非编码RNA（LNCRNA）涉及在包括GC的癌症的发病机制和化学性方面。我们的作品旨在探讨LNCRNA胃癌相关转录物1（GACAT1）在调节GC中调节多柔比星（ADR）和长春脉（VCCR）抗性的作用和分子机制。在本文中，RT-QPCR测定显示GACAT1表达在ADR或VCR抗性GC（SGC7901 / ADR或SGC7901 / VCR）细胞和GC组织中明显减少。 CCK-8测定和流式细胞术分析显示，GACAT1过表达减轻了GC细胞对ADR和VCR的抗性。 RT-QPCR和Western印迹测定公开了GACAT1丧失AKT / MTOR / S6K1信号传导途径并促进了SGC7901 / ADR或SGC7901 / VCR细胞中的PTEN表达。恢复实验证明GACAT1通过调节SGC7901 / ADR或SGC7901 / VCR细胞中的PTEN / AKT / MTOR / S6K1途径来减毒ADR或VCR抗性。在体内实验中表明，GACAT1过表达抑制肿瘤生长，增强了GC异种移植肿瘤模型中的肿瘤生长和增强的ADR-或VCR介导的抗肿瘤作用。这些数据集中在一起，GACAT1通过PTEN / AKT / MTOR / S6K1调节途径在体外和体内削弱了GC细胞对ADR和VCR的抗性，在GACAT1上调时脱落新光作为缓解GC中的化学抑制的潜在策略。

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  • 来源
    《RSC Advances》 |2019年第14期|共8页
  • 作者

    Ding Hengxuan; Sun Junfeng; Li Ruixin; Wang Guojun;

  • 作者单位

    Zhengzhou Univ Affiliated Hosp 1 Dept Gastrointestinal Surg Jianshe Rd 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Affiliated Hosp 1 Dept Gastrointestinal Surg Jianshe Rd 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Affiliated Hosp 1 Dept Gastrointestinal Surg Jianshe Rd 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Affiliated Hosp 1 Dept Gastrointestinal Surg Jianshe Rd 1 Zhengzhou 450052 Henan Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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