Significance of Thymidylate Synthase Expression for Resistance to Pemetrexed in Pulmonary Adenocarcinoma
作者单位：Department of OncologyJiangsu Province Geriatric Institute
会议名称：《2013华东胸部肿瘤论坛暨第六届浙江省胸部肿瘤论坛》
会议日期：2013年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by research grants from department of public health of Jiangsu Province (H201023) the Nature Science Foundation of Jiangsu Province,China(BK2011842)
关 键 词：Non-small cell lung cancer Pemetrexed Resistance Thymidylate synthase Reduced folate carrier Folypoly-γ-glutamate synthetase
摘 要：Pemetrexed(PEM),a multi-targeted antifolate,is promising clinical activity in non-squamous nonsmall cell lung ***,most patients eventually acquire resistance to *** evaluate the resistant mechanism,we exposed the lung adenocarcinoma cell line A549 to stepwise-increasing pemetrexed concentrations of 1.6,6.4 and 16μm,and established three pemetrexed-resistant lung cancer cell lines;A549/PEM-1.6,A549/PEM-6.4,and A549/PEM-I6 *** inhibition was determined by the 3-[4,5- dimethyl-thizol-2-yl]-2,5-diphenyltetrazolium bromide *** of the genes encoding thymidylate synthase(TS),reduced folate carrier(RFC),and folypoly-7-glutamate synthetase(FPGS) were analyzed by quantitative real-time reverse transcriptase polymerase chain *** three A549 cell lines showed more resistance to PEM(3.7-,17.3-,and 38.0- fold,respectively) than the parental cell line,which also showed cross-resistance to cisplatin,but not to docetaxel,vinorelbine,and *** gene expression was significantly increased in three pemetrexed-resistant cells relative to parental cells in a pemetrexed dose dependent *** knockdown TS expression with siRNA enhanced cytotoxicity of pemetrexed in A549/ PEM-16 *** contrast,the levels of HFC and FPGS genes expression in A549/PEM-1.6 cells and A549/ PEM-6.4 cells were significantly decreased,whereas the levels of both genes were restored in A549/PEM-16 *** summary,pemetrexed-resistant A549 cells remained sensitive to docetaxel,vinorelbine,and 5-fluorouracil .TS expression appeared to be associated with resistance to pemetrexed,which may be a predictive marker for pemetrexed sensitivity in lung adenocarcinoma.