| ZHANG Min,REN Jun,XU Bo,et al.Effect of radiation combined with p53 gene therapy and endostatin on mouse prostate cancer[J].Chinese Journal of Radiological Medicine and Protection,2009,29(3):259-263 |
| Effect of radiation combined with p53 gene therapy and endostatin on mouse prostate cancer |
| Received:November 21, 2008 |
| DOI：10.3760/cma.j.issn.0254-5098.2009.03.003 |
| KeyWords:Prostate cancer Genetherapy rAd p53 Endostatin Radiation |
| FundProject:国家自然科学基金 (30670619) |
| Author Name | Affiliation | | ZHANG Min | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | REN Jun | 北京大学临床肿瘤学院、北京肿瘤医院暨北京市肿瘤防治研究所乳腺内科、恶性肿瘤发病机制及转化研究教育部重点实验室 | | XU Bo | 北京大学临床肿瘤学院、北京肿瘤医院暨北京市肿瘤防治研究所乳腺内科、恶性肿瘤发病机制及转化研究教育部重点实验室 | | GAO Xian-shu | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | HE Zhi-song | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | HE Xiao-ming | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | ZHANG Ming | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | LIU Chao-xing | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | HE Xin-yong | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | CAO Guang-ming | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China | | ZHANG Shao-long | Department of Medical Oncology, Peking University First Hospital, Beijing, 100034, China |
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| Abstract:: |
| Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism.Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1×1vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneally accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry.Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P=0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P<0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P=0.000). The expression of Ki67 in groups B and C were equal (P>0.05) and increasing (P=0.000), respectively. Group D had a up-down-up curve (P<0.05),but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P<0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P<0.05).Conclusions The limitation of radiotherapy could be overcome by combination with both p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other. |
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