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5-Fu抗结肠癌作用与细胞凋亡及P-gp蛋白表达的关系

The Antineoplastic Effect of 5-Fu on Human Colorectal Cancer Correlated With the Apoptosis and the Expression of P-gp

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【作者】 谭晖李一琴张志伟周秀田曾希曹建国

【Author】 TAN Hui,LI Yi-qin,ZHANG Zhi-wei,et al (Pathology Department of Nanhua University, Hengyang, Hunan 421001,China)

【机构】 南华大学病理教研室南华大学肿瘤研究所南华大学肿瘤研究所 湖南衡阳421001湖南衡阳421001湖南衡阳421001

【摘要】 目的探讨5-氟尿嘧啶(5-Fu)抗结肠癌作用中,细胞凋亡与P-gp(P-glycoprotein)蛋白表达的关系。方法应用琼脂培养MTT法,测定人结肠癌对抗代谢药的药物敏感性,同时观察5-Fu对结肠癌病人手术前化疗疗效;用S-P免疫组化和图像定量分析技术,测定34例人结肠癌组织中P-gp蛋白表达量;采用末端标记法(TUNEL),检测结肠癌细胞的凋亡指数。结果(1)P-gp蛋白表达量与5-Fu抗药指数呈正相关(r=0.675,P<0.05)。(2)凋亡率与5-Fu抗药指数呈负相关(r=-0.53,P<0.05)。(3)以5-Fu抗药指数1.0为界,>1为耐药组,<1为敏感组,两组间P-gp蛋白表达量、凋亡指数差异均有显著性(P<0.05)。结论5-Fu通过诱导细胞凋亡产生抗结肠癌作用,而P-gp蛋白高表达阻碍5-Fu诱导的凋亡。

【Abstract】 Objective To investigate the relationship between the expression of P-gp protein and the apoptosis induced by 5-fluorouracil (5-Fu) on human colorectal cancer cell. Methods The agar cultured MTT assay was used to examine the sensitivity of human colorectal canaer cell to antimetabolities, and the respone of patients treated with 5-Fu before the operation was observed. The expression of P-gp in 34 cases of human colorectal cacer issue was proved by streptavidin-peroxidase (S-P) immunohistochemcal method and the positive reaction were analysed by picture analysis system ,the TUNEL assay was used to observe the apoptosis of human colorectal cancer cell. Results (1)there was inverse correlation between the expression of P-gp and resistance index of antimetabolitites. (2)There was inverse correlation between index of apoptosis and resistance index of antimetabolities. (3)Classify the group according to the resistance index of 5-Fu which is equal to 1, >1 belongs to the group of resistance, <1 belongs to the group of sensitivity, the difference of expression of P-gp and apoptosis between two groups is significant. Conclusion The antineoplastic effect of 5-Fu on human colorectal cancer may be involved in apoptosis, overexpression of P-gp is associated with resistance to 5-Fu -induced apoptosis.

【关键词】 大肠肿瘤P-gp蛋白5-氟尿嘧啶凋亡
【Key words】 colorectal cancerP-gp5-fluorouracilapoptosis
  • 【文献出处】 南华大学学报(医学版) ,Journal of Nanhua University(Medical Edition) , 编辑部邮箱 ,2005年03期
  • 【分类号】R735.35
  • 【被引频次】7
  • 【下载频次】186
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