Basical Research of Drug Resistant Mechanis in a Human Drug Resistant Ovarian Cancer cell line.

以人卵巢癌生殖细胞来源细胞系（JOHYL-1）为研究对象，将抗肿瘤药物阿霉素(ADM)-、顺铂(CDDP)-、碳喹(CQ)-和长春新碱(VCR)-分别以10^<-6> μ /ml的浓度培养，逐渐增加浓度，CQ、ADM和VCR的浓度从10^<-1> μ /ml增加到10^<-2> μ /ml， CDDP的浓度为10^<-1> μ /ml。对获得的每个耐药细胞群进行了生物学特性检测。1)耐药细胞在不同药物培养72小时后，IC_<50>（杯/毫升），CQ为3.2 × 10^<-3>， ADM为5.8 × 10^<-2>， VCR为1.1 × 10^<-1>， CDDP为2.5，认为耐药细胞比JOHYL-1细胞耐药28-78倍。2) cq耐药细胞倍增时间为38 h， adm耐药细胞倍增时间为58 h， vcr耐药细胞倍增时间为31 h， cdp耐药细胞倍增时间为30 h，明显大于johyl的相应值。1.3)DNA直方图研究提示cdp耐药细胞具有DNA损伤修复机制。4)对其他抗癌药物的交叉耐药研究表明，CDDP耐药细胞对ADM和CDDP耐药细胞无获得性交叉耐药证据。5)连续测定cddp耐药细胞的倍增时间、IC_<50>（马克杯/毫升）和耐药比，并测定裸鼠体内植入后这些参数的变化。结果分别为26小时、4.4 × 10^<-1>和14小时。由此可见，耐药细胞的耐药性在生物学特性上已大大降低，目前正在研究中。

Using a human ovarian cancer cell line of germ cell origin (JOHYL-1), Adriamycin(ADM)-, Cisplatinum(CDDP)-, Carboquon(CQ)- and Vincristine (VCR)- resistant cells were produced by culturing the cells with these anticancer drugs at 10^<-6> mu/ml initially, with the concentration boing then increased stepwise by 10^<-1> mug/ml up to 10^<-2> mug/ml for CQ, ADM and VCR and 10^<-1> mug/ml for CDDP. Each of the resistant cells population thus obtained were examined for their biological properties.1) The drug-resistant cells, when exposed in culture to respective drugs for 72 hours, gave IC_<50> (mug/ml) of 3.2 x 10^<-3> for CQ, 5.8 x10^<-2> for ADM, 1.1 x 10^<-1> for VCR and 2.5 for CDDP, thus being thought to 28-78 times more resistant than JOHYL-1 cells.2) The doubling time was 38 hes for CQ-resistant cells, 58 hrs for ADM-resistant cells, 31 hrs for VCR-resistant cells and 30 hrs for CDDP-resistant cells, thus being definitely longer than the corresponding value for JOHYL-1.3) Study of DNA histograms suggested that CDDP-resistant cells are provided with a DNA damage-respairing mechanism.4) Study of cross resistance to other anticancer drugs showed that CDDP-resistant cells to ADM and ADR-resistant cells to CDDP were no evidence of acquired cross resistance.5) CDDP-resistant cells were measured serially for the doubling time, IC_<50> (mug/ml) and resistance ratio and also determined for changes in these parameter after being implanted in nude mice. The obtained results were 26 hrs, 4.4 x 10^<-1> and 14, respectively. It became thus obvious that the drug resistance of CDDP-resistant cells were greatly diminished in biologic property is currently being investigated.