Screening and Identification of MicroRNAs Related to Acquired Gefitinib-resistance 
in Lung Adenocarcinoma Cell Lines

Abstract

Background and objective Acquired gefitinib-resistance was closely related to inefficiency of EGFR-TKI treatment in lung adenocarcinoma. However, it was not clear that how microRNAs influenced the acquired gefitinib-resistance in lung adenocarcinoma. The aim of this study is to screen and identify the microRNAs correlated with the acquired gefitinib -resistance in lung adenocarcinoma. Methods Morphological difference was observed in gefitinib-sensitive lung adenocarcinoma cell line PC9 cell line and gefitinib-resistance lung adenocarcinoma cell line PC9/AB11 cell line derived from PC9 cell line. Cell cycles and doubling time were detected by flow cytometry, IC50 of gefitinib was evaluated by MTT assay. The differential microRNAs related to acquired gefitinib-resistance were screened and identified by microRNA array and real-time PCR. Results There were obvious morphological differences between PC9 and PC9/AB11 cells. The doubling time, distribution of cell cycle, and the IC50 between PC9 and PC9/AB11 were significantly different. In microarray analysis, compared with PC9 cell line, 4 up-regulated microRNAs were found in PC9/AB11 cells, 9 down-regulated microRNAs were found in PC9/AB11 cells. Real-time PCR revealed that miR-138 was significantly down-regulated in PC9/AB11 cells, accord with the microarray. Conclusion MicroRNAs are involved in acquired Gefitinib-resistance of lung adenocarcinoma. Our data presented here to provide an experimental basis and theory thereunder for further study of effect and molecule mechanism underlying the acquired gefitinib-resistance of lung cancer.

Keywords

• Lung neoplasms
• microRNAs
• Gefitinib
• Aquired-resistance