BACKGROUND Icotinib has been widely used in patients with non-small cell lung cancer (NSCLC), and have significantly enhanced the overall survival rate of NSCLC patients. However, acquired drug resistance limits its clinical efficacy. Tumor cell-derived exosomes have been reported to participate in various biological processes, including tumor invasion, metastasis and drug resistance. MATERIALS AND METHODS In the present study, drug resistance was measured by MTT assay. Exosomes were extracted from the cell supernatant using ultracentrifugation and identified by exosomal marker. HCC827 cells were treated with exosomes derived from icotinib-resistant (IR) HCC827 to observe the invasion and migration of parent cells. The expression of exo-mRNA was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR). In addition, 10 exo-mRNAs detecting from the plasma and bronchoalveolar lavage fluid (BALF) of NSCLC patients with icotinib treatment were used to establish a new drug resistant-warning formula. RESULTS The oncogene MET into exosomes was identified from icotinib-resistant lung cancer cells, and this was also presented in exosomes in NSCLC patients diagnosed with cancer metastasis after icotinib treatment. The knockdown of MET in exosomes significantly decreased the ability of invasion and migration in HCC827 cells. CONCLUSION It was suggested that MET might be specifically package and transferred by exosomes to modify the invasion and migration ability of the surrounding icotinib-sensitive cells.

中文翻译：

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耐依科替尼的HCC827细胞产生具有MET癌基因mRNA的外来体，并介导NSCLC的迁移和侵袭。

背景技术伊科替尼已被广泛用于非小细胞肺癌（NSCLC）患者，并显着提高了NSCLC患者的整体生存率。但是，获得性耐药性限制了其临床疗效。据报道，肿瘤细胞来源的外泌体参与了各种生物学过程，包括肿瘤浸润，转移和耐药性。材料与方法在本研究中，通过MTT测定法测量耐药性。使用超速离心从细胞上清液中提取外泌体，并通过外泌体标记进行鉴定。将HCC827细胞用源自抗艾替尼（IR）HCC827的外泌体处理，以观察亲代细胞的侵袭和迁移。通过逆转录-定量聚合酶链反应（RT-PCR）分析exo-mRNA的表达。此外，从接受icotinib治疗的NSCLC患者的血浆和支气管肺泡灌洗液（BALF）中检测出10种exo-mRNA，以建立新的耐药警告配方。结果从耐icotinib的肺癌细胞中鉴定到外泌体中的致癌基因MET，这也存在于受icotinib治疗后被诊断为癌症转移的NSCLC患者的外泌体中。外泌体中MET的敲低显着降低了HCC827细胞的侵袭和迁移能力。结论提示MET可能被外来体特别包装并转移，以改变周围可替丁敏感性细胞的侵袭和迁移能力。