No.1 Radiotherapy Department, Yantaishan Hospital, Yantai City, China.
No.1 Radiotherapy Department, Yantaishan Hospital, Yantai City, China.
Eur J Pharmacol. 2018 Aug 15;833:79-85. doi: 10.1016/j.ejphar.2018.04.021. Epub 2018 Apr 25.
Forkhead box protein M1 (FOXM1), an important regulator of tumorigenesis in various human tumors, has recently been reported to play a role in the modulation of radiosensitivity in glioma and breast cancer cells. The present study aimed to investigate the effects of FOXM1 on radiotherapy resistance in human lung cancer and to explore the related molecular mechanisms. The results revealed that FOXM1 expression was upregulated in A549 and H1299 cells after IR (Ionizing radiation). FOXM1 inhibition impeded survival fractions, impeded proliferation, and triggered apoptosis after IR. Moreover, the silencing of FOXM1 dampened cell migration, invasion, and EMT (epithelial-mesenchyman transition) in A549 and H1299 cells treated by IR. In addition, KIF20A was also highly expressed in IR-treated A549 cells and downregulated by FOXM1 inhibition. Knockdown of KIF20A inhibited the survival fraction. Reintroduction of KIF20A partly reversed the effects of FOXM1 on the proliferation, apoptosis, and metastasis of A549 cells. Taken together, these results indicated that FOXM1 might enhance radioresistance partly through the induction of KIF20A expression.
叉头框蛋白 M1（FOXM1）是多种人类肿瘤中肿瘤发生的重要调节因子，最近有研究报道其在调节脑胶质瘤和乳腺癌细胞放射敏感性方面发挥作用。本研究旨在探讨 FOXM1 对人肺癌放疗抵抗的影响及其相关分子机制。结果表明，IR（电离辐射）后 A549 和 H1299 细胞中 FOXM1 表达上调。FOXM1 抑制可阻碍 IR 后的存活分数、增殖，并触发细胞凋亡。此外，IR 处理的 A549 和 H1299 细胞中，FOXM1 沉默可抑制细胞迁移、侵袭和 EMT（上皮-间充质转化）。此外，KIF20A 在 IR 处理的 A549 细胞中也高度表达，并被 FOXM1 抑制下调。KIF20A 的敲低抑制了存活分数。KIF20A 的重新引入部分逆转了 FOXM1 对 A549 细胞增殖、凋亡和转移的影响。综上所述，这些结果表明 FOXM1 可能通过诱导 KIF20A 表达来增强放射抵抗性。
