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Titolo:
IN-VITRO SYNERGY OF PACLITAXEL (TAXOL) AND VINORELBINE (NAVELBINE) AGAINST HUMAN-MELANOMA CELL-LINES
Autore:
PHOTIOU A; SHAH P; LEONG LK; MOSS J; RETSAS S;
Indirizzi:
CHARING CROSS HOSP,DEPT MED ONCOL,CATHERINE GRIFFITHS CANC RES LAB,MELANOMA UNIT LONDON W6 8RF ENGLAND CHARING CROSS & WESTMINSTER MED SCH,DEPT HISTOPATHOL LONDON W6 8RF ENGLAND
Titolo Testata:
European journal of cancer
fascicolo: 3, volume: 33, anno: 1997,
pagine: 463 - 470
SICI:
0959-8049(1997)33:3<463:ISOP(A>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHASE-II TRIAL; MALIGNANT-MELANOMA; ANNULATE LAMELLAE; MITOTIC BLOCK; VINBLASTINE; VINDESINE; INVITRO; MECHANISM; PROLIFERATION; INHIBITION;
Keywords:
MELANOMA; PACLITAXEL; VINORELBINE; ISOBOLOGRAMS; DRUG COMBINATIONS; TUBULIN IMMUNOFLUORESCENCE; ANNULATE LAMELLAE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
A. Photiou et al., "IN-VITRO SYNERGY OF PACLITAXEL (TAXOL) AND VINORELBINE (NAVELBINE) AGAINST HUMAN-MELANOMA CELL-LINES", European journal of cancer, 33(3), 1997, pp. 463-470

Abstract

Paclitaxel (PTXL) (Taxol), a taxane, and vinorelbine (VRB), a semisynthetic vinca alkaloid drug, have tubulin as their common intracellulartarget, but inhibit growth by binding to different sites. We evaluated in vitro the antiproliferative activity of these two drugs as singleagents and in combination, against two human melanoma cell lines, G361 and StMl11a. The SRB (sulphorhodamine B) assay was used ao determinegrowth inhibition. Possible drug-drug interaction at the cellular level was assessed by constructing Isoboles (Isobologram analysis) and applying the concept of an 'envelope of additivity'. Both agents were active in the nanomolar range at clinically achievable concentrations, The mean IC50 for G361 was 46.6 nM (PTXL) and 19.9 nM. (VRB) after a 1 h drug exposure. Mean IC50 (1 h) for StMl11a was 9.7 nM (PTXL) and 26.9 nM (VRB). Isobole analysis at the isoeffect levels of 25%, 50% and 75% indicated that drug interaction was predominantly synergistic (supra-additive) when paclitaxel and VRB were added concurrently for 1 h tocultures of StM11 1a or G361. In some experiments, this synergy was observed with particularly low concentrations of paclitaxel (3 nM) and VRB (0.01 nM). A few points were located within the envelope of additivity or in the subadditive (antagonism) region of the isobole. An overall synergy was also found if the data were analysed by the median effect analysis. The effect of these agents on the cytoskeleton and ultrastructure were studied with immunofluorescence and electron microscopy, respectively. These results confirm the in vitro inhibitory activityof paclitaxel and VRB against malignant melanoma, but more importantly the two drugs appear to act synergistically at relatively low concentrations. (C) 1997 Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 02:39:29