FKBP51 induces p53-dependent apoptosis and enhances drug sensitivity of human non-small-cell lung cancer cells
FKBP51 induces p53-dependent apoptosis and enhances drug sensitivity of human non-small-cell lung cancer cells
复制标题
FKBP51 诱导 p53 依赖性细胞凋亡并增强人非小细胞肺癌细胞的药物敏感性。
DOI：
10.3892/etm.2020.8450
复制
发表时间：
2020-03-01
影响因子：
2.7
通讯作者：
Wu, Xiushan
中科院分区：
文献类型：
--
作者：
Chen, Yu;Liu, Zhiqiang;Wu, Xiushan
肺癌是世界上最常见的癌症类型之一，非小细胞肺癌（NSCLC）占所有肺癌病例的85%左右。尽管非小细胞肺癌的发病率很高，但其发病机制尚不清楚。本研究探讨了fk506结合蛋白51 （FKBP51）在NSCLC发展中的作用，并确定了FKBP51修饰用于NSCLC治疗的相关因素。免疫组化分析FKBP51在人NSCLC组织样本中的表达。流式细胞术观察过表达fkbp51的A549细胞的凋亡情况。采用双荧光素酶报告基因法证实FKBP51与p53表达的相关性，采用western blotting分析FKBP51对p53信号通路的影响。最后，使用细胞计数试剂盒-8测定细胞活力。结果提示FKBP51在人肺癌中下调。此外，fkbp51过表达的A549细胞的凋亡率可能增加。此外，FKBP51促进了p53的表达和随后p53信号通路的激活。这些结果表明FKBP51通过p53信号通路促进A549细胞凋亡。此外，FKBP51增强了A549细胞对顺铂的敏感性。总的来说，这些数据表明FKBP51可以作为人类肺癌的生物标志物，因此可以在未来将其纳入NSCLC治疗中。
Lung cancer is one of the most prevalent cancer types worldwide, and non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Despite the notable prevalence of NSCLC, the mechanisms underlying its progression remain unclear. The present study investigated the involvement of FK506-binding protein 51 (FKBP51) in NSCLC development and determined the factors associated with FKBP51 modification for NSCLC treatment. Immunohistochemical analysis was performed to analyze FKBP51 expression in human NSCLC tissue samples. Additionally, flow cytometry was performed to observe the apoptosis of FKBP51-overexpressing A549 cells. A dual-luciferase reporter assay was performed to confirm the association between FKBP51 and p53 expression, and western blotting was performed to analyze the effects of FKBP51 on the p53 signaling pathway. Finally, cell viability was measured using a Cell Counting Kit-8 assay. The results suggested FKBP51 downregulation in human lung cancer. Furthermore, apoptosis rates may be increased in FKBP51-overexpressing A549 cells. Moreover, FKBP51 promoted p53 expression and subsequent p53 signaling pathway activation. These results indicated that FKBP51 promoted A549 cell apoptosis via the p53 signaling pathway. Additionally, FKBP51 enhanced the sensitivity of A549 cells to cisplatin. Collectively, these data suggested that FKBP51 could serve as a biomarker for human lung cancer and can thus be tailored for incorporation into NSCLC therapy in the future.