Anticancer drug sensitivity profiles of new and established melanoma cell lines.
Metastatic melanoma is notable for its resistance to chemotherapy, and methods for determining resistance in cultures would be advantageous. We investigated the chemosensitivities of seven newly derived low passage lines and eight established melanoma lines. A 96-well microculture system utilising [3H]-thymidine incorporation was used to determine IC50 values (50% inhibitory concentrations) for lomustine, mitomycin C, 4-hydroperoxycyclophosphamide, cisplatinum, 5-fluorouracil, vincristine, doxorubicin, etoposide, amsacrine and the amsacrine analogue CI-921. Cytokinetic parameters were determined using 5-bromodeoxyuridine and flow cytometry. The presence of "transport" and "atypical" multidrug resistance was investigated with an IC50 ratio method, using pairs of drugs with differing sensitivity to these multidrug resistance mechanisms. A wide range of chemosensitivity for each of the antitumor agents was observed, and a spectrum of activity was observed in each of the assays for multidrug resistance. Unexpectedly, a number of cell lines displayed coordinate sensitivity or resistance to cytotoxic agents with unrelated mechanisms of action. Resistance mechanisms apart from "transport" and "atypical" multidrug resistance may be required to account for the observed 40-fold range in overall chemosensitivity of the melanoma lines.
Marshall
E S
ES
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Holdaway
K M
KM
Shaw
J H
JH
Finlay
G J
GJ
Matthews
J H
JH
Baguley
B C
BC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001973:Bromodeoxyuridine