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 expressing 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 assay and western blot assay. Cell survival was assessed using a clonogenic assay. TUNEL assay was used in determination of apoptosis. Four human gastric carcinoma cells infected with Adp53 were irradiated with 4Gy and cell cycle distribution and Sub-G1 peak were assayed by flow cytometry. Results: G2/M arrest, apoptosis and inhibition of tumor cell proliferation were induced by infection at Adp53 at 100 MOI which caused high transfer rate of wild-type p53 and strong expression of p53 protein in four human gastric carcinoma cells. The radio-enhancement ratio of Adp53 at 4Gy were 3.0 for W cell, 3.6 for M cell, 2.2 for neo cell and 2.5 for 823 cell in vitro. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and radiosensitivity of human gastric carcinoma cell lines in vitro independently on cellular intrinsic p53 status thus supporting the combination of p53 gene therapy with radiotherapy in clinical trials.
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Zhang SW, Xiao WQ, Lü YY. Role of p53 tumor suppressor gene in radiosensitivity of human gastric carcinoma cell lines (in Chinese) [J]. Chin J Radiat Oncol 1999; 8:116.
Li JH, Lax SA, Kim J, et al. The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma [J]. Int J Radiat Oncol Biol Phys 1999; 3:607.
Geng L, Walter S, Melian E, et al. Transfection of a vector expressing wild-type p53 into cells of two human glioma cell lines enhances radiation toxicity (in Chinese) [J]. Radiat Res 1998; 1:31.
Clayman GL, el-Naggar AK, Lippman SM, et al. Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma [J]. J Clin Oncol 1998; 6:2221.
Swisher SG, Roth JA, Nemunaitis J, et al. Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer [J]. J Natl Cancer Inst 1999; 91:763.
Reiser M, Neumann I, Schmiegel W, et al. Induction of cell proliferation arrest and apoptosis in hepatoma cells through adenoviral-mediated transfer of p53 gene [J]. J Hepatol 2000; 5:771.
Brand K, Klocke R, Possling A, et al. Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection [J]. Gene Ther 1999; 6:1054.
Qiu ZH, Lao MF, Wang YF, et al. The expression of multi-genes via a recombinant adenovirus and their effects of inducing apoptosis on lung cancer cells (in Chinese) [J]. Chin J Cancer Biother 1999; 6:83.
Kanegae Y, Makimura M, Saito I. A simple and efficient method for purification of infections recombinant adenovirus [J]. Jpn J Med Sci Biol 1994; 47:157.
He P, Tang ZY, Ye SL. The expression and localization of wild-type p53-GFP fused gene on human high-metastasis hepatocellular carcinoma cell line (in Chinese) [J]. Chin J Hepatol 2000; 8:105.
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Foundation item: This work was supported by the National Natural Science Foundation of China (No. 39670234).
Biography: ZHANG Shan-wen (1946–), male, professor, Department of Radiotherapy, Peking University School of Oncology, majors in radiation oncology.
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Zhang, Sw., Xiao, Sw. & Lü, Yy. Effect of adenovirus-mediated p53 gene transfer on apoptosis and radiosensitivity of human gastric carcinoma cell lines. Chin. J. Cancer Res. 15, 14–18 (2003). https://doi.org/10.1007/s11670-003-0004-4
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DOI: https://doi.org/10.1007/s11670-003-0004-4