Department of Respiratory, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Department of Oncology, the First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), Jiaxing, PR China.
J Drug Target. 2020 Mar;28(3):300-306. doi: 10.1080/1061186X.2019.1650368. Epub 2019 Aug 5.
Afatinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been approved as EGFR, HER2, HER3 and HER4 inhibitor for non-small cell lung cancer (NSCLC) treatment. However, acquired resistance to afatinib has been found in most EGFR mutant NSCLC patients. Bladder cancer associated transcript 1 (BLACAT1) is a novel long non-coding RNAs (lncRNA) that play a functional role as an oncogenic lncRNA and is associated with chemoresistance. We aimed to identify the role of BLACAT1 in afatinib-resistant NSCLC and underlying mechanisms. Afatinib-resistant NSCLC cells were established. MTT assay, colony formation assay, apoptosis analysis, qRT-PCR and western blot analysis, immunohistochemistry, and in vivo study were carried out. BLACAT1 was up-regulated in afatinib-resistant NSCLC cells. Knockdown of BLACAT1 reversed the resistance of afatinib to NSCLC cells by modulating STAT3 signalling. The results provided a potential strategy for afatinib-resistant NSCLC by targeting BLACAT1.
阿法替尼是第二代不可逆的表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），已被批准用于治疗非小细胞肺癌（NSCLC）的 EGFR、HER2、HER3 和 HER4 抑制剂。然而，大多数 EGFR 突变型 NSCLC 患者对阿法替尼产生了获得性耐药。膀胱癌相关转录物 1（BLACAT1）是一种新型的长链非编码 RNA（lncRNA），作为一种致癌 lncRNA 发挥功能，与化疗耐药性相关。我们旨在确定 BLACAT1 在阿法替尼耐药性 NSCLC 中的作用及其潜在机制。建立了阿法替尼耐药性 NSCLC 细胞系。进行了 MTT 测定、集落形成测定、凋亡分析、qRT-PCR 和 Western blot 分析、免疫组织化学和体内研究。BLACAT1 在阿法替尼耐药性 NSCLC 细胞中上调。BLACAT1 的敲低通过调节 STAT3 信号转导逆转了 NSCLC 细胞对阿法替尼的耐药性。该结果为针对 BLACAT1 的阿法替尼耐药性 NSCLC 提供了一种潜在的策略。
