The Study for Non-cross Resistant Alternating Chemotherapy for Bladder Cancer

人膀胱癌亲本细胞株T24(CL-7)以递增浓度的顺铂(CDDP)作用20个月，建立了顺铂耐药细胞系CL-7/CDDP。克隆形成实验表明，CL-7/CDDP对CDDP的耐药性是CL-7的2.7倍。比较CL-7/CDDP和CL-7细胞的生物学和生化特性。两种细胞系在倍增时间和培养效率上无明显差异，但在染色体数目模式上有较小差异。CDDP作用后两株细胞内CDDP浓度无明显差异，但CL-7/CDDP细胞内谷胱甘肽(GSH)和金属硫蛋白(MT)水平升高。用克隆形成法检测了CL-7/CDDP对其他抗癌药物的敏感性，并与PAR-…进行了比较。更好的细胞系，CL-7。根据耐药程度的不同，这些药物可分为3类：对顺铂具有同等抗药性的药物(CDDP衍生物、MMC、VP-16)、对细胞无耐药性的药物(ADM、CTX、IFO、VLB)和增强细胞杀伤作用的药物(5-FU、MTX)。顺铂类药物对DWA-2114R的抗性程度最高，CBDCA、NK-121和254-S的抗性程度依次降低。为确定抗癌药物在裸鼠体内的抗肿瘤作用，将10~7个/只的CL-7和CL-7/CDDP细胞分别接种于裸鼠皮下，当估计瘤重达到100 mg时，给予抗癌药物。各剂量顺铂2 mg/kg、4 mg/kg、8 mg/kg，每5天3次。CDDP 8 mg/kg组可抑制CL-7和CL-7/CDDP肿瘤的生长，但CL-7/CDDP肿瘤对CDDP的耐药性不明显。对于CL-7/CDDP肿瘤，肿瘤生长非常缓慢，肿瘤重量在个体动物之间的分散性很大，这一点有待于改善，这表明这三组药物进行非交叉耐药交替化疗的可能性。较少

A cis-diamminedichloroplatinum(CDDP)-resistant cell line, CL-7/CDDP, has been established by chronic exposure of a parent human bladder cancer cell line, T24(CL-7), to CDDP at progressively increaced concentration for twenty months. CL-7 /CDDP was 2.7-fold more resistant to CDDP than CL-7 as determined by colony formation assay. Biological and biochemical characteristics were examined in CL-7/CDDP to compare with CL-7. There were no differences in doubling time and plating efficiency between the two cell lines, but a small one in the mode of chromosome numbers. Intra-cellular CDDP concentration after CDDP exposure showed no difference between the two cell lines, but CL-7/CDDP showed a higher glutathione(GSH)and metallothionein(MT)level. It is suggested that the mechanism of acquired resistance to CDDP is attributed to intra-cellular detoxication, but not to the efflux.The sensitivity of CL-7/CDDP for other anticancer drugs were examined by colony formation assay to compare with the par … More ent cell line, CL-7. Consequently, these drugs could be classified into 3 groups according to the degree of resistance ; drugs with an equal degree of resistance to that of CDDP(CDDP derivatives, MMC, VP-16), drugs for which the cells showed no resistance(ADM, CTX, IFO, VLB), and drugs whose cytocidal effects were enhanced(5-FU, MTX). The degree of resistance in the CDDP derivatives was the highest in DWA-2114R, decreesing in the following order in CBDCA, NK-121, and 254-S.An in vivo study was also performed. To determine the anti-tumor effects of anti-cancer drugs in nude mice, CL-7 and CL-7/CDDP cells of 10^7/body each were inoculated subcutaneouly, and the anti-cancer drug was administered intraperitoneally, when estimated tumor weight reached 100mg. Each dose of 2mg/kg, 4mg/kg, or 8mg/kg of CDDP was administered 3 times every 5 days. The inhibition of tumor growth was observed in the CDDP 8mg/kg group with the CL-7 and CL-7/ CDDP tumor, but the resistance to CDDP in the CL-7/CDDP tumor was not clear. Concerning the CL-7/CDDP tumor, the tumor growth was very slow and the dispertion of tumor weight among individual animals was large, which had to be improved.These results indicated the possibility of non-crosss resistant alternating chemotherapy using these three groups of drugs. Less