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5-Aza-CdR enhances sensitivity of human non-small cell lung cancer cells to gefitinib and its mechanisms
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Abstract:
Objective:To explore the effect of DNA methylation inhibitor 5-Aza-2’-deoxycytidine (5-Aza-CdR) on enhancing the sensitivity of human non-small cell lung cancer (NSCLC) cells to gefitinib and its mechanisms. Methods: EGFR mutant NSCLC cell line H1650 and EGFR wild type NSCLC cell line H1299 were used in this study. The changes in sensitivity of H1650 and H1299 cells to gefitinib after 5-Aza-CdR treatment were detected by CCK-8 assay. The expression levels of miR-200c and epidermal growth factor receptor (EGFR) mRNA were evaluated by real-time PCR. Results: EGFR mutant and wild type NSCLC cell lines H1650 and H1299 showed a certain degree of drug resistance to gefitinib. The sensitivity of H1650 and H1299 cells to gefitinib ncreased after 5-Aza-CdR treatment, with IC50 value of gefitinib to cells decreasing significantly (\[1.04±0.35\] vs \[159.37±17.48\] μmol/L, \[6.28±1.02\] vs \[223.76±23.63\] μmol/L, P<0.01). Real-time PCR assay results showed that the expression level of miR-200c was increased in EGFR mutant H1650 cells or wild type H1299 cells after 5-Aza-CdR treatment (\[0.009±0.003\] vs \[0.002±0.001\], \[0.004±0.001\] vs 0, P<0.01), respectively. Besides, the expression level of EGFR mRNA was significantly increased compared with 5-Aza-CdR untreated group (\[0.286±0.037\] vs \[0.015±0.012\], \[0.057±0014\] vs \[001±0.01\], P<0.01). Conclusion: The expressions of miR-200c and EGFR mRNA in human NSCLC H1650 and H1299 cells are up-regulated by DNA methylation inhibitor 5-Aza-CdR, which increases the sensitivity of H1650 and H1299 cells to gefitinib.
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Project Supported:
Project supported by the Research Foundation of Science and Techenology Bureau of Jiangsu Province (No. BK2009446), and the Wu Jieping Medical Foundation (No. 320.6700.09050)
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