Cui Yujie, Zhu Tienian, Song Xuejing, Liu Jiankun, Liu Shuang, Zhao Ruijing
Department of Oncology, Hebei Medical University, Shijiazhuang 050017, Hebei, China; Department of Oncology, Hebei Genenral Hospital, Shijiazhuang 050051, Hebei, China.
Department of Immunology, Hebei Medical University, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang 050017, Hebei, China; Department of Medical Oncology, Bethune International Peace Hospital, Shijiazhuang 050082, Hebei, China.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):733-739. doi: 10.1016/j.bbrc.2017.11.075. Epub 2017 Nov 12.
Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, have shown notable effects in lung adenocarcinoma patients harboring EGFR mutations, there are significant differences between individual patients in the degree of benefits provided by EGFR-TKIs. Some evidence supports a role for caveolin-1 (Cav-1) in modulating drug sensitivity. This study aimed to investigate whether Cav-1 plays an important role in sensitivity to EGFR-TKIs in lung adenocarcinoma cells. Downregulation of Cav-1 in PC-9 cells were performed to investigate changes in sensitivity to EGFR-TKIs in vitro and in vivo. Knockdown of Cav-1 dramatically enhanced sensitivity to EGFR-TKIs by down-regulating phosphorylation of EGFR. These results suggest that Cav-1 may be a predictor of the poor efficacy of EGFR-TKIs treatment in lung adenocarcinoma with EGFR mutations.
尽管表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs），包括吉非替尼和厄洛替尼，已在携带EGFR突变的肺腺癌患者中显示出显著疗效，但EGFR-TKIs给个体患者带来的获益程度存在显著差异。一些证据支持小窝蛋白-1（Cav-1）在调节药物敏感性方面发挥作用。本研究旨在调查Cav-1在肺腺癌细胞对EGFR-TKIs的敏感性中是否起重要作用。通过下调PC-9细胞中的Cav-1来研究体外和体内对EGFR-TKIs敏感性的变化。敲低Cav-1通过下调EGFR的磷酸化显著增强了对EGFR-TKIs的敏感性。这些结果表明，Cav-1可能是EGFR-TKIs治疗EGFR突变型肺腺癌疗效不佳的一个预测指标。
