Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer.
Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer.
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发表时间：
2010-12
影响因子：
2
通讯作者：
H. Imai;K. Kaira;N. Oriuchi;K. Shimizu;H. Tominaga;N. Yanagitani;N. Sunaga;T. Ishizuka;S. Nagamori;K. Promchan;T. Nakajima;N. Yamamoto;M. Mori;Y. Kanai
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作者：
H. Imai;K. Kaira;N. Oriuchi;K. Shimizu;H. Tominaga;N. Yanagitani;N. Sunaga;T. Ishizuka;S. Nagamori;K. Promchan;T. Nakajima;N. Yamamoto;M. Mori;Y. Kanai
l型氨基酸转运蛋白1 （LAT1）在多种人类肿瘤中高表达。分析了抑制LAT1在非小细胞肺癌（NSCLC）中的抗肿瘤活性。材料与方法采用RT-PCR法检测54株肺癌细胞株中LAT1 mRNA的表达。将lat1,2 -氨基双环-(2,2,1)-庚烷-2-羧酸（BCH）抑制剂给予H1395细胞。研究了51例非小细胞肺癌患者的LAT1表达与临床特征和预后的关系。结果BCH抑制LAT1可降低H1395细胞活力。此外，吉非替尼与BCH联合使用比单独使用任何一种药物更能降低细胞的活力。抑制LAT1可降低mTOR、p70S6K和4EBP1的磷酸化水平。LAT1蛋白表达与野生型EGFR密切相关，是预测预后不良的独立显著因素。结论抑制LAT1可能是有效治疗非EGFR突变NSCLC的新原理。
BACKGROUND L-type amino acid transporter 1 (LAT1) is highly expressed in various human neoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Expression of LAT1 mRNA in 54 lung cancer cell lines was examined by RT-PCR. An inhibitor of LAT1, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), was administered to H1395 cell. LAT1 expression was examined in correlation with clinical features and outcome in 51 NSCLC patients. RESULTS Inhibition of LAT1 by BCH reduced cell viability in H1395 cells. Furthermore, co-administration of gefitinib with BCH reduced the viability of the cells more than either agent alone. Inhibition of LAT1 reduced the level of phosphorylation of mTOR, p70S6K and 4EBP1. LAT1 protein expression was closely associated with wild type EGFR, and was an independent significant factor to predict a poor prognosis. CONCLUSION Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.