Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Anticancer Res. 2010 Dec;30(12):4819-28.
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).
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.
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.
Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.
L 型氨基酸转运蛋白 1（LAT1）在各种人类肿瘤中高度表达。本研究分析了抑制 LAT1 在非小细胞肺癌（NSCLC）中的抗肿瘤活性。
通过 RT-PCR 检测 54 株肺癌细胞系中 LAT1 mRNA 的表达。用 LAT1 的抑制剂 2-氨基双环[2.2.1]-庚烷-2-羧酸（BCH）处理 H1395 细胞。在 51 例 NSCLC 患者中，将 LAT1 的表达与临床特征和预后相关联进行分析。
BCH 抑制 LAT1 可降低 H1395 细胞的活力。此外，与单独使用任一药物相比，吉非替尼与 BCH 联合使用可降低细胞活力。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，是预测不良预后的独立显著因素。
抑制 LAT1 可能为无 EGFR 突变的 NSCLC 提供一种新的有效治疗策略。
