Depleted Aldehyde dehydrogenase1A1 reverses cisplatin resistance of non-small cell lung cancer cells A549/DDP
作者单位：Department of Geriatrics The First Affiliated Hospital of Nanjing Medical University
会议名称：《2015年老年医学学术年会》
会议日期：2015年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：aldehyde dehydrogenase1A1 cisplatin resistance apoptosis non-small cell lung cancer A549/DDP cells
摘 要：Object Cisplatin is the first-line chemotherapy for the treatment of non-small cell lung cancer(NSCLC). However, its resistance has been a major obstacle in the management of NSCLC. Aldehyde dehydrogenase1A1(ALDH1A1) over-expression has been observed in a variety of cancers, including lung cancer. The purpose of our study was to investigate the effect of ALDH1A1 expression on cisplatin resistance and explore the responsible mechanism. Method To measure its potential role in cisplatin resistance, a short hairpin RNA(sh RNA) was used to knockdown ALDH1A1 expression. The cell viability of A549/DDP cells was detected by MTT, and phosphorylation level of AKT was detected by western blot *** In this study, we found that ALDH1A1 is over-expressed in cisplatin resistant cells A549/DDP compared with its parental cells A549. The ALDH1A1 depletion significantly decreased A549/DDP proliferation(0.89±0.06 vs 0.69±0.02, con vs sh, P0.05) and reduced cisplatin resistance( 71.92±2.56 vs 47.10±1.99, con vs sh,P0.05). Besides, PI3K/Akt pathway was activated in A549/DDP, and ALDH1A1 knockdown reduced phosphorylation level of AKT. Moreover, the combination of ALDH1A1-sh RNA and PI3K/Akt pathway inhibitor LY294002 markedly inhibited cell viability(0.69±0.02 vs 0.35±0.00, sh vs sh+LY, P0.001) and increased sensitivity of resistant cells to cisplatin(38.19±1.23 vs 47.10±1.99,sh+LY vs sh, P0.05). Conclusion These data suggested that ALDH1A1 depletion could reverse cisplatin resistance in human lung cancer cell line A549/DDP, and may act as a potential target for the treatment of lung cancers resistant to cisplatin .