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抑癌基因p53对人胃癌细胞系放射敏感性的作用

Role of p53 tumor suppressor gene in radiosensitivity of human gastric carcinoma cell lines

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【作者】 张珊文肖卫群吕有勇

【Author】 ZHANG Shanwen, XIAO Weiqun, LU Youyong. Department of Radiotherapy, School of Oncology, Beijing Medical University, Beijing 100034

【机构】 北京医科大学临床肿瘤学院放射治疗科

【摘要】 目的评价野生型抑癌基因(正常)p53对人胃癌细胞系放射敏感性的控制作用。方法用流式细胞仪分析4Gy照射后8和24小时4种不同p53状态的人胃癌细胞系细胞周期分布和凋亡的反应。以4Gy细胞存活份数和10Gy照射后的肿瘤生长曲线比较4种细胞的放射敏感性。结果照射4Gy后8小时和24小时的p53正常的BGC823细胞出现强烈的G1期阻滞(分别占原细胞总数的67.9%和61.1%),比无照射的该细胞G1期比例有显著的增高(P<0.05),并出现明显的预示凋亡的亚G1峰(SubG1),凋亡细胞比例分别达13.0%和15.3%;同样条件下其他3种p53异常的细胞G1期比例没有显著的变化(P>0.05),都没有出现亚G1峰,凋亡细胞比例均为0.0%。p53正常的BGC823细胞4Gy的存活份数明显低于其它3种细胞(P<0.05);且细胞移植肿瘤10Gy照射后比其它3种的生长受到更明显抑制(P<0.05)。结论以上的结果证实了野生型p53基因促进了照射后肿瘤细胞的G1期阻滞和凋亡,从而明显地提高肿瘤细胞的放射敏感性。

【Abstract】 Objective To assess the role of p53 tumor suppressor gene ( wildtype p53 ) in radiosensitivity of human gastric carcinoma cell lines. Methods Cell cycle distribution and apoptosis were analyzed by flow cytometry of four human gastric carcinoma cell lines with different p53 statuses at H 8 and H 24 following irradiation of 4Gy. Surviving fraction of the four cell lines after 4 Gy irradiation was counted. Relative volume of implanted tumor of the four cell lines in nude mice was observed after irradiation of 10Gy. Results The BGC823 cells (wtp53) containing normal p53 showed strong arrest in G1 phase at H 8 and H 24 following 4 Gy irradiation (67.9% and 61.1% of original population) while the other three cell lines contained unnormal p53 had no arrest in G1 in H 8 and H 24 following irradiation at 4Gy. In the BGC823 cells (wtp53), a sub G1 peak of apoptosis was observed at H 8 and H 24 after 4 Gy irradiation, apoptotic cell rate 13.0% and 15.3% respectively. The other three cell lines gave no apoptotic response at H 8 and H 24 following 4 Gy irradiation.Surviving fraction of BGC823 cells (wtp53) radiated at 4Gy significantly smaller than other three cell lines’ ( P <0.05). Tumor of BGC823 cells (wtp53) after 10 Gy irradiation was significantly was inhibited than the other three cell lines ( PTBZ<0.05). Conclusions These results suggest that wildtype p53 promotes G1 phase arrest and apoptosis of tumor cells following irradiation and,therefore, enhances intrinsic radiosensitivity of tumor cells.

【基金】 国家自然科学基金
  • 【文献出处】 中华放射肿瘤学杂志 ,CHINESE JOURNAL OF RADIATION ONCOLOGY , 编辑部邮箱 ,1999年02期
  • 【分类号】R735.2
  • 【被引频次】34
  • 【下载频次】115
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