| WU Guang-yin,HAN Qian,ZHU Qing-yao,LI Liang,LI Xin.Radiosensitization of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts[J].Chinese Journal of Radiological Medicine and Protection,2013,33(4):376-379 |
| Radiosensitization of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts |
| Received:January 31, 2013 |
| DOI：10.3760/cma.j.issn.0254-5098.2013.04.010 |
| KeyWords:Esophageal carcinoma Insulin-like growth factor-1 receptor Radiosensitivity |
| FundProject: |
| Author Name | Affiliation | E-mail | | WU Guang-yin | Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou 450003, China | | | HAN Qian | Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou 450003, China | | | ZHU Qing-yao | Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou 450003, China | | | LI Liang | Department of Oncology Radiotherapy, Henan Provincial People's Hospital, Zhengzhou 450003, China | | | LI Xin | 郑州大学第一附属医院肿瘤科 | zsc2686@yahoo.com.cn |
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| 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 with control group with no treatment; irradiation group with 8 Gy 6 MV X-rays 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 group: receiving both 30 μg/(kg·d)-1 AG1024 /em>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 (CyclinD1) 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 accumulated in 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. |
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