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LncRNAH19 的抑制作用具有抗肿瘤作用,并能增强非小细胞肺癌体内对 Gefitinib 和化疗的敏感性。

Inhibition of LncRNAH19 has the effect of anti-tumour and enhancing sensitivity to Gefitinib and Chemotherapy in Non-small-cell lung cancer in vivo.

机构信息

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

J Cell Mol Med. 2020 May;24(10):5811-5816. doi: 10.1111/jcmm.15245. Epub 2020 Apr 13.

Abstract

Lung cancer is one of the most common malignant diseases, which ranked first in both men and women malignancies worldwide. The survival rate of non-small-cell lung cancer (NSCLC) has been limited with distant metastasis and shortage of effective chemotherapeutics in recent years. Thus, novel therapeutic strategies for NSCLC are urgently explored. Here, we showed that inhibition of H19 effectively inhibited the progression of NSCLC. Moreover, down-regulation of H19 treatment significantly enhanced the levels of PTEN and PDCD4, while suppressed the expressions of NFIB in NSCLC. Furthermore, down-regulation of H19 combined with Gefitinib treatment significantly increased the levels of PTEN and PDCD4, while decreased the expression levels of NFIB. Moreover, the results showed that Gefitinib treatment significantly reduced the shH19-mediated miR-21 expression levels. Our results showed that down-regulation of H19 combined with Gefitinib administration significantly improved the effect of shH19 treatment alone on the progression of NSCLC, which was involved in the activation of PTEN signalling pathway in NSCLC in vivo. Therefore, these findings might indicate a novel molecular mechanism, which could provide a new potential combination of therapeutic method in NSCLC.

摘要

肺癌是最常见的恶性疾病之一,在全球范围内无论是男性还是女性,其癌症发病率均位居首位。近年来,非小细胞肺癌(NSCLC)的转移和缺乏有效化疗药物的问题仍然存在,导致其生存率受到限制。因此,迫切需要探索治疗 NSCLC 的新策略。本研究表明,抑制 H19 可有效抑制 NSCLC 的进展。此外,下调 H19 的治疗可显著提高 PTEN 和 PDCD4 的水平,同时抑制 NSCLC 中 NFIB 的表达。此外,下调 H19 联合吉非替尼治疗可显著增加 PTEN 和 PDCD4 的水平,同时降低 NFIB 的表达水平。此外,结果表明,吉非替尼治疗可显著降低 shH19 介导的 miR-21 表达水平。本研究结果表明,下调 H19 联合吉非替尼给药可显著提高 shH19 治疗单独对 NSCLC 进展的疗效,这与体内 NSCLC 中 PTEN 信号通路的激活有关。因此,这些发现可能表明存在一种新的分子机制,可为 NSCLC 提供一种新的潜在联合治疗方法。

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