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

人类耐药卵巢癌细胞系耐药机制的基础研究。

基本信息

批准号：
61570810
负责人：
YASUDA Makoto
金额：
$ 1.47万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570810/
关键词：
Ovarian cancer cell cell culture resistant cell antitumor drug Ovarian cancer germ cell tumor culture cell Restant ratic CDDP耐性細胞制癌剤 DNAヒストグラム細胞増殖曲線 Ovarian carcinoma cancer resistanu

项目摘要

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.

使用生殖细胞来源的人卵巢癌细胞系（JOHYL-1），通过将细胞与这些抗癌药物以10 μ g/ml的初始浓度培养，产生阿霉素（ADM）-、顺铂（CDDP）-、卡波昆（CQ）-和长春新碱（VCR）-抗性细胞<-6>，然后将浓度逐步增加10 μ <-1>g/ml，<-2>对于CQ、ADM和VCR达到10 μ g/ml，对于CDDP达到10 μ <-1>g/ml。结果表明：（1）细胞对CQ、ADM、VCR和CDDP的IC_<50>（μ g/ml）分别为3.2 × 10 <-3>~（-1）、5.8 × 10 ~（-1）<-2>、1.1 × 10 ~（-1）和2.5，是JOHYL-1细胞的28-78倍;（2）细胞倍增时间CQ为38 hes，ADM为58 h<-1>，VCR抗性细胞为31小时，CDDP抗性细胞为30小时，3）DNA直方图研究表明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的耐药率明显高于对照组。对CDDP耐药的细胞没有获得性交叉耐药的证据。5）连续测定CDDP耐药细胞的倍增时间、IC_<50>（μ g/ml）和耐药率，并测定这些参数在裸鼠体内移植后的变化。获得的结果分别为26小时、4.4 × 104<-1>和14。因此，很明显，CDDP抗性细胞的抗药性在生物学特性上大大降低，目前正在研究。