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目的 通过建立人卵巢癌体外耐药模型，研究卵巢癌对顺铂的耐药机制。方法应用顺铂连续作用并逐步提高药量的递增压力选择法，从人卵巢腺癌细胞ＣＯＣ１中分离出对顺铂耐药的细胞亚株（ＣＯＣ１／ＤＤＰ），并比较耐药细胞和亲代细胞某些生物学特性差异。结果ＣＯＣ１／ＤＤＰ细胞对顺铂的耐药性是ＣＯＣ１的６．５倍，群体倍增时间较亲代细胞缩短了１２．９％。对卡铂和丝裂霉素Ｃ有不同程度的交叉耐药性，对阿霉素和５－氟尿嘧啶则保持敏感。并且耐药细胞内铂离子含量及ＤＮＡ链间交联指数均明显低于ＣＯＣ１细胞，但免疫细胞化学显示ＣＯＣ１及ＣＯＣ１／ＤＤＰ细胞内均无Ｐ糖蛋白表达。结论ＣＯＣ１／ＤＤＰ细胞对顺铂耐药的主要原因是细胞内药物浓度降低及ＤＮＡ链间交联形成减少，与Ｐ糖蛋白关系不大。
Objective To establish a drug resistance model of ovarian cancer in vitro to study the mechanism of resistance to cisplatin in ovarian cancer. Methods Cisplatin - resistant subtypes (COC1 / DDP) were isolated from human ovarian adenocarcinoma COC1 cells by cisplatin - induced continuous dose - escalation and incremental pressure selection. Drug resistant cells and parental cells were compared Some differences in biological characteristics. Results The resistance of COC1 / DDP cells to cisplatin was 6.5 times that of COC1, and the population doubling time was 12.9% shorter than that of the parental cells. There is varying degrees of cross-resistance to carboplatin and mitomycin C, and doxorubicin and 5-fluorouracil remain sensitive. The content of platinum ion and the cross-linking index between DNA chains in drug-resistant cells were significantly lower than those in COC1 cells, but immunocytochemistry showed no expression of P-glycoprotein in COC1 and COC1 / DDP cells. Conclusions The main reason of COC1 / DDP cell resistance to cisplatin is the decrease of intracellular drug concentration and the decrease of cross-linking between DNA chains, which is not related to P-glycoprotein.