Wang Di, Gao Lichen, Liu Xueting, Yuan Chuang, Wang Guihua
Department of Oncology, Changsha Central Hospital, Changsha, Hunan 410004, P.R. China.
Department of Pharmacy, Changsha Central Hospital, Changsha, Hunan 410004, P.R. China.
Oncol Lett. 2017 Jul;14(1):1105-1108. doi: 10.3892/ol.2017.6208. Epub 2017 May 19.
The aim of the present study is to investigate if rapamycin is a radiosensitizer of nasopharyngeal carcinoma (NPC), and to identify which pathways are involved in radiation sensitization. , using untreated cells as the control, NPC cells were treated with rapamycin, ionizing radiation (IR) or both. Differences in the phosphorylation of ribosomal protein S6 and glycogen synthase kinase (GSK) 3β, expression of cyclin D1, clonogenic survival, number of phosphorylated histone subunit 2AX (γH2AX) foci, and cell cycle status between the study groups were compared. The results indicated that rapamycin alone decreased the phosphorylation of S6 and GSK3β, as well as the expression of cyclin D1, in NPC cells. Thus, rapamycin-treated NPC cells had lower cell viability, and higher DNA damage and G1 arrest than control cells. In addition, the combination of rapamycin and IR caused the highest cell death, DNA damage and G1 arrest when compared with the effects caused by either treatment alone. In conclusion, rapamycin improves the anti-tumor effect of IR for treating NPC through inhibiting the Akt/mechanistic target of rapamycin/S6 and Akt/GSK3β/cyclin D1 signaling pathways.
本研究的目的是探究雷帕霉素是否为鼻咽癌(NPC)的放射增敏剂,并确定哪些信号通路参与放射增敏作用。以未处理的细胞作为对照,用雷帕霉素、电离辐射(IR)或两者对NPC细胞进行处理。比较各研究组之间核糖体蛋白S6和糖原合酶激酶(GSK)3β的磷酸化、细胞周期蛋白D1的表达、克隆形成存活率、磷酸化组蛋白亚基2AX(γH2AX)焦点数量以及细胞周期状态的差异。结果表明,单独使用雷帕霉素可降低NPC细胞中S6和GSK3β的磷酸化以及细胞周期蛋白D1的表达。因此,与对照细胞相比,经雷帕霉素处理的NPC细胞具有较低的细胞活力、较高的DNA损伤和G1期阻滞。此外,与单独使用任一处理方法相比,雷帕霉素与IR联合使用导致的细胞死亡、DNA损伤和G1期阻滞最为严重。总之,雷帕霉素通过抑制Akt/雷帕霉素作用靶点/S6和Akt/GSK3β/细胞周期蛋白D1信号通路,增强了IR治疗NPC的抗肿瘤效果。