CYTOTOXICITY OF PACLITAXEL AND DOCETAXEL IN HUMAN NEUROBLASTOMA CELL-LINES

被引:35
作者
RICCARDI, A
SERVIDEI, T
TORNESELLO, A
PUGGIONI, P
MASTRANGELO, S
RUMI, C
RICCARDI, R
机构
[1] UNIV CATTOLICA SACRO CUORE, DIV PEDIAT ONCOL, I-00168 ROME, ITALY
[2] UNIV CATTOLICA SACRO CUORE, DEPT MED SEMEIOT, I-00168 ROME, ITALY
关键词
PACLITAXEL; DOCETAXEL; NEUROBLASTOMA; CELL LINES; CYTOTOXICITY;
D O I
10.1016/0959-8049(95)00056-O
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Taxanes are an important new class of anticancer agents that inhibit cell division by the unique mechanism of increasing the rate of microtubule assembly and preventing microtubule depolymerisation. Using the colony inhibition assay, we compared the cytotoxicity of paclitaxel and docetaxel in three human neuroblastoma (NB) cell lines, SH-SY5Y, BE(2)M17 and CHP100. Different exposure times (3, 6, 12, 24, 48 and 72 h) and different concentrations ranging from 0.1 nM to 10 mu M were tested. Both paclitaxel and docetaxel show antineoplastic activity in human NE cell lines. Taxanes' antitumour activity varied among the different cell lines, CHP100 being the most sensitive and SH-SY5Y the least sensitive. Paclitaxel cytotoxicity appears schedule-dependent, with marked cell kill observed only for exposures of 24 h or longer. Docetaxel cytotoxicity was dependent upon prolonged exposure only in the SH-SY5Y cell line, while an exposure time of 3-6 h resulted in exponential cell kill in the other two cell. lines. Docetaxel was more cytotoxic than paclitaxel with a mean ratio of (paclitaxel/docetaxel) IC50 values ranging from 2 to 11. For both taxanes, we observed good correlation between cytotoxic effect and percentage of cells blocked in G2/M phase. A cytotoxic effect occurred at concentrations comparable with those achieved in the plasma of patients treated with these agents in initial clinical trials. The full potential of prolonged infusion or repeated daily administrations of taxanes should be explored in clinical studies, and responses to taxanes in neuroblastoma should be assessed in paediatric phase II studies.
引用
收藏
页码:494 / 499
页数:6
相关论文
共 25 条
[1]  
ARBUCK SG, 1993, SEMIN ONCOL, V20, P31
[2]  
BISSERY MC, 1991, CANCER RES, V51, P4845
[3]  
BISSETT D, 1993, CANCER RES, V53, P523
[4]  
ETTINGER DS, 1993, SEMIN ONCOL, V20, P46
[5]  
EXTRA JM, 1993, CANCER RES, V53, P1037
[6]  
FROMES Y, 1992, Proceedings of the American Association for Cancer Research Annual Meeting, V33, P511
[7]   PHASE-II TRIAL OF TAXOL, AN ACTIVE-DRUG IN THE TREATMENT OF METASTATIC BREAST-CANCER [J].
HOLMES, FA ;
WALTERS, RS ;
THERIAULT, RL ;
FORMAN, AD ;
NEWTON, LK ;
RABER, MN ;
BUZDAR, AU ;
FRYE, DK ;
HORTOBAGYI, GN .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1991, 83 (24) :1797-1805
[8]  
HURWITS CA, 1993, J CLIN ONCOL, V11, P2234
[9]   COMPARATIVE INVITRO CYTOTOXICITY OF TAXOL AND TAXOTERE AGAINST CISPLATIN-SENSITIVE AND CISPLATIN-RESISTANT HUMAN OVARIAN-CARCINOMA CELL-LINES [J].
KELLAND, LR ;
ABEL, G .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1992, 30 (06) :444-450
[10]  
LEGHA SS, 1990, CANCER, V65, P2478, DOI 10.1002/1097-0142(19900601)65:11<2478::AID-CNCR2820651114>3.0.CO