Radiosensitization of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the effect of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts and the underlying mechanisms.Methods The mouse model was established by injecting EC9706 cells subcutaneous in nude mice.When the tumors were 100 mm3 in size,the mice were divided into 4 groups randomly withcontrol group with no treatment; irradiation group with 8 Gy 6 MV Xrays at 1 and 8 d each time; AG1024-treatment group with 30 μg/(kg-d) AG1024 injected intraperitoneally (ip) 5 times a week for two weeks ; combination groupreceiving both 30 μg/(kg· d)-1 AG1024 ip and irradiation of 8 Gy X-rays.The diameters of the tumors were measured every 3 days.The mice were sacrificed and the weights of tumors were measured at 15 d after treatment.Tumor inhibition rate was calculated.The cell cycle was examined by flow cytometry.The expression of cell cycle protein D1 (CyclinDl) of the tumors were detected by immunohistochemical staining.Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used to detect the cell apoptosis in the tumor tissue.Results The tumor weight in the irradiation group,AG1024-treatment group and combination group were significantly decreased compared with the control group,and the inhibition rate were 39.16％,18.73％,57.04％,respectively (F =13.566,P ＜ 0.05).After treatment with AG1024 and irradiation,tumor tissue cells were significantly accumulatedin the G0/G1 and G2/M phases and decreased in S phase compared to the irradiation group (t =-6.654,-16.738,12.871,P ＜ 0.05).The CyclinD1 expression of the combination group was significantly decreased compared with the control group.In the combination group,the apoptotic cells were detected by TUNEL assay.Conclusions IGF-1R inhibitor AG1024 could change the cell cycle and induce cell apoptosis,which might result in the enhancement of radiosensitivity on the esophageal cancer xenografts.