大肠癌对顺铂、5-氟尿嘧啶、羟基喜树碱的敏感性与P-糖蛋白表达的研究

Research of primary drug resistance of colorectal carcinoma to hydroxycamptothecin?cisplatin and 5-fluorouracil、with corelation of It's p-glycoprotein expression

目的 探讨大肠癌对羟基喜树碱 (HCPT)、顺铂 (CDDP)、5 氟尿嘧啶 (5 Fu)的敏感性与P 糖蛋白 (P gp)表达之间的相关性。方法 MTT法检测 37例大肠癌细胞的药物敏感性 ,流式细胞技术 (FCM )检测其P gp表达 ,数据按中效原理计算。 结果 大肠癌对CDDP、5 Fu单药或加CDDP的敏感性与P gp表达阳性率增加而降低 ;而对HCPT单药或加CDDP或 5 Fu的高敏、中敏、不敏感各组间P gp表达无明显差别。大肠癌的耐药系娄在HCPT的CDDP或 5 Fu联用时降低 ,但在CDDP与 5 Fu联用时增加。结论 大肠癌对CDDP、5 Fu的敏感性与P gp表达程度呈负相关 ,而对HCPT的敏感性与P gp表达无明显相关性。HCPT与CDDP或 5 Fu联用对大肠癌的抑制有协同作用 ,而 5 Fu +CDDP则达不到协同或相加作用。

Objective To evaluate the the correlation between the percentage of P gp positive cells and the sensitivity of colorectal carcinoma cells to hydroxycamptothecin?cisplatin and 5 Fluorouracil.Methods Flow cytometry (FCM) was used to detect P gp, and MTT to assay the sensitivity to chemotherapeutics. The median effect principle was used to calculate the concentration(μmol/ml) of single drug and two drug combination when 50% of cancer cells were inhibited (LC50). Results The sensitivity of colorectal cancer cells to 5 Fu?CDDP or 5 Fu+CDDP decreased while their P gp expression increased,but their P gp expression almost had no different among the arms of high?middle and non sensitivity.Conclusion The sensitivity of colorectal carcinoma to CDDP?5 Fu correlated reversely with the percentage of P gp positive cells,but didn′t correlated to HCPT.The use of HCPT plus CDDP or 5 Fu achieved synergetic action to suppress the colorectal cancer cells,but 5 Fu plus CDDP didn′t achieved synergetic action. Key words:colorectal carcinoma;p glycoprotein; hydroxycamptothecin; cisplatin; 5 fluorouracil