Queen Mary School, Nanchang University, Nanchang, Jiangxi, China (mainland).
Department of Emergency Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).
Med Sci Monit. 2020 Apr 10;26:e922148. doi: 10.12659/MSM.922148.
BACKGROUND Sorafenib, which is a multitargeted kinase inhibitor, has shown some antitumor effects in patients with non-small cell lung cancer (NSCLC). However, the potential target of sorafenib's antitumor activity is largely unknown. Moreover, definitive predictive biomarkers of benefit have rarely been reported. MATERIAL AND METHODS The alteration in inhibitor of differentiation 1 (ID1) expression in NSCLC cells with sorafenib treatment was detected by western blotting. The sensitivity of NSCLC cells to sorafenib was observed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. Loss-of-function and gain-of-function experiments were performed to observe the role of ID1 expression in epithelial to mesenchymal transition (EMT) progression. RESULTS Initially, we observed that ID1 was downregulated in NSCLC cells treated with sorafenib. The response of NSCLC cells to sorafenib was inhibited by the transfection of small interfering RNAs (siRNAs) targeting ID1. In contrast, the transfection of ID1-overexpressing plasmids improved the response of NSCLC cells to sorafenib. Further experiments indicated that ID1 is expressed at high levels in epithelial H460 cells and expressed at low levels in mesenchymal H358 cells. Loss-of-function and gain-of-function experiments suggested that ID1 negatively regulates EMT in NSCLC. CONCLUSIONS The expression of ID1 is dose-dependently inhibited by sorafenib, and the overexpression of ID1 contributes to the antitumor activity of sorafenib by suppressing EMT development. Our results indicate that ID1 might be a potential target for the antitumor activity of sorafenib in NSCLC and that targeting ID1 is a feasible strategy to improve the sensitivity of NSCLC cells to sorafenib.
索拉非尼是一种多靶点激酶抑制剂，已显示出对非小细胞肺癌（NSCLC）患者的一些抗肿瘤作用。然而，索拉非尼抗肿瘤活性的潜在靶点在很大程度上尚不清楚。此外，很少有报道明确的获益预测生物标志物。
通过 Western blot 检测索拉非尼处理后 NSCLC 细胞中分化抑制因子 1（ID1）表达的变化。通过 MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑）测定观察 NSCLC 细胞对索拉非尼的敏感性。进行功能丧失和功能获得实验以观察 ID1 表达在上皮间质转化（EMT）进展中的作用。
最初，我们观察到索拉非尼处理的 NSCLC 细胞中 ID1 下调。针对 ID1 的小干扰 RNA（siRNA）转染抑制了 NSCLC 细胞对索拉非尼的反应。相反，ID1 过表达质粒的转染改善了 NSCLC 细胞对索拉非尼的反应。进一步的实验表明，ID1 在上皮 H460 细胞中高表达，在间充质 H358 细胞中低表达。功能丧失和功能获得实验表明，ID1 负调控 NSCLC 中的 EMT。
ID1 的表达被索拉非尼剂量依赖性抑制，ID1 的过表达通过抑制 EMT 发展有助于索拉非尼的抗肿瘤活性。我们的结果表明，ID1 可能是索拉非尼在 NSCLC 中抗肿瘤活性的潜在靶点，靶向 ID1 是提高 NSCLC 细胞对索拉非尼敏感性的可行策略。
