ZHANG Shan-wen,XIAO Shao-wen,YANG Jing-xian.Adenovirus-mediated p53 gene transfer increases radiosensitivity of human gastric carcinoma cells[J].Chinese Journal of Radiological Medicine and Protection,2004,24(4):308-311 |
Adenovirus-mediated p53 gene transfer increases radiosensitivity of human gastric carcinoma cells |
Received:August 15, 2003 |
DOI: |
KeyWords:Gastric carcinoma Radiotherapy Adenovirus-mediated p53 gene |
FundProject:国家自然科学基金资助项目(39670234) |
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Abstract:: |
Objective To evaluate the effect of adenovirus-mediated p53 gene (Adp53) on apoptosis and radiosensitivity of human gastric carcinoma cell lines. Methods Recombinant adenovirus carrying wild-type p53 gene was transferred into four human gastric carcinoma cell lines with different p53 genetic status. P53 protein expression was detected by immunohistochemistry and Western blot assay. Cell survival was assessed using a clonogenic assay. TUNEL assay was used in determination of apoptosis. The four human gastric carcinoma cell line infected with Adp53 were irradiated with 4 Gy, and cell cycle distribution and apoptotic rate were assayed by flow cytometry. Nude mice xenograft models of W and M cell were intratumorally injected with Adp53 and 48 h later were irradiated with 6 Gy. Relative volume in growth curve of tumor was used to observe tumor regression. Results G2/M arrest, apoptosis and inhibition of tumor cell proliferation were induced by infection with Adp53 at 100 MOI, which caused high transfer rate of wild-type p53 and strong expression of P53 protein in the four human gastric carcinoma cell line cells. When evaluating radio-biologic efficacy by apoptotic rate, the apoptotic enhencement ratio of Adp53 at 4 Gy was 3.0 for W cell, 3.6 for M cell, 2.2 for neo cell and 2.5 for 823 cell respectively, in vitro. The antitumor enhencement ratio of Adp53 at 6 Gy was 1.41 for W cell-implanted tumor and 1.91 for M cell-implanted tumor in vivo. Conclusion This study demonstrated that Adp53 transfer increased cellular apoptosis and radiosensitivity of human gastric carcinoma. |
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