Secretomic analysis uncovers the mechanisms of gefitinib resistance in non-small-cell lung carcinoma

Abstract

For 2 decades, lung cancer has been the most deadly of all malignant neoplasms in Taiwan. Novel strategies for the discovery and treatment of lung cancers are becoming a particularly important research topic in the field of biomedicine. Gefitinib (trade name Iressa; AstraZeneca, Wilmington, DE, USA) is a biologic agent used to treat lung cancer. The clinical antitumor action of gefitinib is primarily the inhibition of the epidermal growth factor receptor. Gefitinib is indicated as a first-line therapy for lung cancer, although the occurrence of chemoresistance limits the longterm results of this drug. This study was divided into two research directions. The first part is to generate the drug-resistant cancer cell line as a platform to understand the mechanism of drug inactivation of gefitinib for lung cancer. The second part is to collect cell secretomes to find potential biomarkers for the diagnosis and treatment of lung cancer by using minimally invasive assays. Therefore, the non-small-cell lung carcinoma line PC9 and gefitinib-resistant cancer cell line PC9/gef were used in this study. With the analysis of secretomics, differentially expressed extracellular secreted proteins were identified to study the desired biomarkers for molecular diagnostics and gefitinib-resistance. These cell lines provide a useful tool for the further study of the biologic properties in lung cancer in vitro.