Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, R.O.C. Division of Hematology-Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
School of Medicine, Tzu Chi University, Hualian, Taiwan, R.O.C. Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
Anticancer Res. 2014 Jun;34(6):2927-35.
Inhibition of mammalian target of rapamycin (mTOR) kinase enhances the radiosensitivity of some cancer cells. We investigated the effect of RAD001, an mTOR inhibitor, on irradiated oral cancer cell lines.
Clonogenic assays were performed to determine the radiosensitivity of SCC4 and SCC25 cells after treatment with RAD001. Target protein phosphorylation, apoptosis, and cell-cycle progression were assessed in SCC4 cells treated with RAD001 with and without ionizing radiation.
RAD001 increased the radiosensitivity of SCC4 cells without affecting cell death; it also inhibited phosphorylation of mTOR, S6, and factor 4E binding protein 1 and reduced the clonogenic survival of irradiated cancer cells. RAD001 combined with radiation increased G2 arrest by activating CHK1, which phosphorylates CDC25C at Ser216, thereby inhibiting CDC2-cyclin B 1 complex formation.
RAD001 enhances the radiosensitivity of SCC4 cells by inhibiting mTOR signaling and inducing G2 cell-cycle arrest through disruption of the G2 checkpoint.
哺乳动物雷帕霉素靶蛋白（mTOR）激酶的抑制增强了一些癌细胞的放射敏感性。我们研究了 mTOR 抑制剂 RAD001 对放射治疗的口腔癌细胞系的影响。
采用集落形成实验检测 RAD001 处理后 SCC4 和 SCC25 细胞的放射敏感性。检测 RAD001 联合和不联合电离辐射处理 SCC4 细胞后靶蛋白磷酸化、细胞凋亡和细胞周期进程。
RAD001 增加 SCC4 细胞的放射敏感性而不影响细胞死亡；它还抑制 mTOR、S6 和 4E 结合蛋白 1 的磷酸化，并降低受照射癌细胞的集落存活能力。RAD001 联合辐射通过激活 CHK1 诱导 G2 期阻滞，CHK1 使 CDC25C 在 Ser216 磷酸化，从而抑制 CDC2-细胞周期蛋白 B1 复合物的形成。
RAD001 通过抑制 mTOR 信号通路并通过破坏 G2 检查点诱导 G2 细胞周期阻滞来增强 SCC4 细胞的放射敏感性。
