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

用生殖细胞来源的人卵巢癌细胞株(JOHYL-1)，以10µ/ml的浓度培养阿霉素(ADM)、顺铂(CDDP)、卡波昆(CQ)和长春新碱(VCR)耐药细胞，然后逐步增加浓度，CQ、ADM、VCR和CDDP的浓度分别增加10和10µg/ml。1)耐药细胞在培养72小时后，对CQ的IC_(50)为3.2×10~(-3)，ADM为5.8×10~(-2)，ADM为1.1×10~(-1)~(-1)；对于VCR和CDDP，因此被认为比JOHYL-1细胞耐药28-78倍。2)倍增时间对于CQ耐药细胞是38HES，对于ADM耐药细胞是58小时，对于VCR耐药细胞是31小时，对于CDDP耐药细胞是30小时，因此，明显长于JOHYL-1.3)DNA直方图的研究表明，CDDP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ADR耐药细胞不是获得性交叉耐药的证据。50-gt；(µg/ml)和耐药率，并测定移植到裸鼠体内后这些参数的变化。获得的结果分别为26小时，4.4×10~(-1)和14。因此，很明显，顺铂耐药细胞的耐药性在生物学特性上大大降低，目前正在进行研究。

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.