Rb功能缺失与人结肠癌细胞对抗代谢药抗性的相关性研究

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目的 探讨人结肠癌细胞对抗代谢药抗性及 5-氟尿嘧啶 ( 5-Fu )术前化疗疗效与Rb蛋白表达之间的关系。方法 应用S -P免疫组化和图像定量分析技术 ,检测 10例人结肠癌组织中Rb蛋白含量 ;同时用琼脂培养MTT法测定人结肠癌细胞对抗代谢药的药物敏感性和观察 5-Fu对结肠癌病人手术前化疗疗效。结果  ( 1) 10例人结肠癌标本中 7例Rb蛋白阳性表达 ,Rb蛋白缺失率 30 % ( 3/10 )。 ( 2 )Rb蛋白表达量 (阳性面积乘以平均光密度 )与人结肠癌细胞对抗代谢药 ( 5-Fu和氨甲喋呤 )抗药指数呈负相关 (r =- 0 .767,P =0 .0 10和r=- 0 .894 ,P <0 .0 0 1)。 ( 3)Rb蛋白表达量与 5-Fu对结肠癌患者手术前化疗疗效积分呈正相关 (r=0 .857,P =0 .0 0 2 )。结论 Rb功能缺失与人结肠癌细胞对抗代谢药抗性相关 Objective To investigate the relationship between anti-metabolite resistance of human colon cancer cells and preoperative chemotherapeutic effect of 5-fluorouracil (5-Fu) and Rb protein expression. Methods S-P immunohistochemistry and image quantitative analysis were used to detect the Rb protein content in 10 human colon cancer tissues. Meanwhile, the drug sensitivity of human colon cancer cells to anti-metabolites was determined by agar culture and the effects of 5-Fu Preoperative Chemotherapy in Patients with Colon Cancer. Results (1) The expression of Rb protein was positive in 7 of 10 human colon cancer specimens, and the rate of Rb protein deletion was 30% (3/10). (2) Rb protein expression (positive area multiplied by average optical density) was negatively correlated with drug resistance index of human colon cancer cells (5-Fu and methotrexate) (r = - 0.767, P = 0. 0 10 and r = - 0 .894, P <0. 001). (3) There was a positive correlation between the expression of Rb protein and the 5-Fu on the score of preoperative chemotherapy in patients with colon cancer (r = 0.857, P = 0.002). Conclusion The loss of Rb function is related to the resistance of human colon cancer cells to anti-metabolites
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