EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest
EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest
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DOI：
10.1016/j.bbrc.2019.09.076
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发表时间：
2019-11-19
影响因子：
3.1
通讯作者：
Kijima, Takashi
中科院分区：
文献类型：
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作者：
Ishigaki, Hirotoshi;Minami, Toshiyuki;Kijima, Takashi
小细胞肺癌（SCLC）是一种神经内分泌肿瘤的特征，由于其生长迅速、早期传播以及对化疗快速获得多药耐药性，是一种临床侵袭性癌症。此外，尽管非 SCLC 的治疗取得了巨大的进步，但 SCLC 的标准化疗方案三十年来没有改变。开发新的 SCLC 治疗策略已成为一个紧迫的问题。我们发现 Eph 受体 A2 (EphA2) 的表达在 13 个 SCLC 细胞系中的 3 个和 76 个 SCLC 肿瘤样本中的 5 个中上调。使用 EphA2 的 siRNA 进行遗传抑制，通过诱导 SBC-5 细胞的细胞周期停滞，显着抑制细胞增殖。此外，EphA2的小分子抑制剂（ALW-II-41-27和达沙替尼）也通过相同的机制专门抑制EphA2阳性SCLC细胞的增殖。总的来说，EphA2 可能是 SCLC 治疗靶点的一个有前途的候选者。 (C) 2019 Elsevier Inc. 保留所有权利。
Small-cell lung cancer (SCLC) is characterized by one of neuroendocrine tumors, and is a clinically aggressive cancer due to its rapid growth, early dissemination, and rapid acquisition of multidrug resistance to chemotherapy. Moreover, the standard chemotherapeutic regimen in SCLC has not changed for three decades despite of the dramatic therapeutic improvement in non-SCLC. The development of a novel therapeutic strategy for SCLC has become a pressing issue. We found that expression of Eph receptor A2 (EphA2) is upregulated in three of 13 SCLC cell lines and five of 76 SCLC tumor samples. Genetic inhibition using siRNA of EphA2 significantly suppressed the cellular proliferation via induction of cell cycle arrest in SBC-5 cells. Furthermore, small molecule inhibitors of EphA2 (ALW-II-41-27 and dasatinib) also exclusively inhibited proliferation of EphA2-positive SCLC cells by the same mechanism. Collectively, EphA2 could be a promising candidate as a therapeutic target for SCLC. (C) 2019 Elsevier Inc. All rights reserved.