胃癌CyclinD1、PTEN表达及与化疗药物耐药性关系的研究

Relationship between Cyclin D1 or PTEN expression and chemoresistance in gastric carcinoma

目的探讨胃癌组织中CyclinDl、PTEN蛋白的表达和与化疗药物敏感性的关系。方法取胃癌手术标本84例,用免疫组化检测CyclinDl、PTEN蛋白在胃癌组织中的表达。并用MTT比色法观察胃癌原代培养细胞在体外对化疗药物HCPT、CDDP、5-Fu、ADM和MMC的敏感性。结果胃癌组织中CyclinDl和PTEN蛋白的阳性率分别为67.86%和46.43%。胃癌细胞对不同化疗药物敏感性不同:5-Fu、MMC和DDP对胃癌细胞的抑制率显著高于ADM和HCPT(P<0.05)。CyclinDl阳性者对5-Fu、HCPT的敏感性显著高于阴性者(P<0.05)。PTEN蛋白表达与五种化疗药物的体外耐药无相关性(P>0.05)。结论CyclinDl蛋白与胃癌对化疗药物敏感性相关,检测其表达对选择化疗药物有实用价值。

Objective To investigate the relationship between CyclinD1,PTEN expression and the the sensitivity to chemotherapeutic-drugs in gastric carcinoma. Methods 84 samples of gastric cancer was collected, CyclinD1, PTEN was detected by immunohistochemistry. Primary single-cell suspensions were prepared from fresh specimens of primary gastric cancer and exposed to hydroxycamptothecin （HCPT）, cisplatin （CDDP）, 5-fluorouracil （5-FU）, adriamycin （ADM） and mitomycin （MMC） respectively for 4.8 h. Cell metabolic activity and rate of inhibition were evaluated by tetrazolium （MTT） assay. Results Positive rate of CyclinD1 and PTEN expressed in gastric cancer was 67.86% and 46.43%, respectively. Chemosensitivity of the gastric cancer cells varied; the rates of inhibition of cells exposed to MMC, CDDP and 5-FU were significantly higher than that of cells exposed to ADM and HCPT （P〈0.05）. Cyclin D1 positive cells showed more sensitive to 5-Fu, HCPT than the negative cells （P〈 0.05）. Conclusion Expression of CyclinD1 was related with primary drug-resistance of gastric cancer, and Cyclin D1 expression detection could be used as predictors in chemotherapeutic drug administration and for identifying drug resistance in gastric carcinoma.