| Summary: | 碩士 === 中國醫藥大學 === 癌症生物學研究所碩士班 === 102 === Lung cancer is one of the most common malignancies worldwide. Epidermal growth factor receptor (EGFR) regulates many biological functions including proliferation, anti-apoptosis and metastasis. A specific EGFR tyrosine kinase inhibitor, gefitinib (Iressa, ZD1839), has been developed to exhibit clinical efficacy in lung cancer patients. However, acquisition of resistance to gefitinib is also observed after treatment. It is critical and timely to understand the molecular mechanisms involved in gefitinib resistance. In this study, we found the RNA expression of VEGF-C was higher in gefitinib resistance PC9 (PC9/GR) cells than wild type PC9 (PC9/WT) cells. Knockdown the VEGF-C in PC9/GR cells re-sensitize to gefitinib; consistently, overexpression of VEGF-C in PC9/WT cells enhanced resistance to gefitinib. In additional, we also found that PC9/GR cells expressed high level of Slug more than PC9/WT cells and related to gefitinib resistance. Furthermore, overexpression of Slug in PC9/GR/shVEGF-C cells enhanced the resistance to gefitinib. Together, our study reveals a molecular mechanism link between Slug and VEGF-C, and provides evidence the Slug and VEGF-C is potential therapeutic targets in gefitinib-resistant lung cancer.
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