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特征和机制。方法应用浓度递增和短时间作用法。从人卵巢癌细胞A2780中培养对顺铂耐药细胞亚株（A2780／DDP）。采用MTT法检测耐药细胞的耐药指数及对抗癌药物的敏感性。而高效液相色谱仪检测耐药细胞内顺铂含量。以及应用RT－PCR法和免疫组化法检测MDRI和GST－π的表达情况。结果（1）A2780／DDP对DDP的耐药倍数为10．59．并且其倍增时间较A2780细胞延长，对VCR、MTX呈高度耐药状态，对Carp、Pym、CTX、VP16有不同程度的耐药，而对ADM、5－FU、KSM无交叉耐药现象。（2）耐药细胞内顺铂含量明显低于A2780细胞。（3）耐药细胞内GST－π的表达呈强阳性，而MDRI只有在高度耐药细胞呈弱阳性。结论A2780细胞对顺铂的耐药是获得性的，并呈多药耐药特征，其耐药的主要原因是与谷胱甘肽解毒途径有关的酶表达增多有关。GST一π表达过度导致细胞内药物浓度降低有关。
To establish cis-platin (DDP)-resistant human ovarian cancer cell line and investigate it'S featureand mechanism reponsible of resistance of DDP. METHODS DDP-resistant human ovarian cancer line (A2780/DDP) was developed by gradually increasing dose and the sensitivity of the anticancer drugs were screened in theA2780/DDP by MTT method. DDP content in the A2780/DDP was screened by High-performance liquid chromatography (HPLC). The polymeras chain reaction (RT-PCR) and the immunohistochemical method were used tomeasure multidrug resistance (MDR1) and Glutathione transferase-π (GST-π). RESULTS (1) A2780/DDP cellswere of 10. 59-fold resistance DDP and displayed high resistance to DDP and displayed high resistance with VCR、MTX, but low resistance with Carp、Pym、CTX、 VP16. No cross-resistance was found to ADM, 5-FU and KSM.(2) DDP content of the A2780/DDP decreased significantly. (3) There was higher over expression of GST-π inA2780/DDP and lower were expression of MDR1 in A2780/DDP with high DDP resistance. CONCLUSIONA2780/DDP cells was acquired and had a characterization of the multidurg resistance. The primary factor of causing A2780/DDP resistance to DDP is correlate overexpression of GST-π and the reductive intracellular content ofDDP.
出处
《中国癌症杂志》
CAS
CSCD
1998年第3期187-189,共3页
China Oncology
关键词
卵巢肿瘤
顺铂
药物耐受性
细胞株
Ovarian neoplasms
Drug resistance
Cisplatin cell line
