【摘要】 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。更多还原

【Abstract】 Objective To establish cisplatin (DDP ) -resistant subline of human ovarian cancer and inveatigate the mechanism responsible for resistance to DDP. Methods A DDP-resistant human ovarian adenocar- cinoma cell subline (COC1 /DDP ) was developed by contineous stepwise selection in increasing concentra- tion of DDP from the parent cell line COC1 in vitro. The multiple changes of biological. properties in COC1 /DDP cell line were determined. Results COC1 /DDP cells were of 6. 5 - fold resistance to DDP and displayed significant cross-resistant with carplatin and mitomycin C , but still remained sensitive to 5-fluorouracil and adriamycin. A. compared to the parent cells , in COC1 /DDP cells , the doubling time was reduced by 1 2. 9% . Cellular content of DDP was diminished by more one half and the DNA-inter- strand cross-links (ISC ) was lower than that of the sensitive cells. Evidence of P-glycoprotein overex- pression was not shown in COC. and COC1 /DDP cell lines by means of immunohistochemical method . Conclusions The primary factor causing COC1 /DDP resistance to DDP is the reduction of intracellular platinum accumulation and DNA ISC formation. The resistance is not considered to be associated with the multidrug resistant and P-glycoprotein.更多还原