Concentration and sequence dependent synergism of ethyldeshydroxy‐sparsomycin in combination with antitumor agents
作者:
H Hofs,
D Wagener,
V de Valk-Bakker,
H van Rennes,
H Ottenheijm,
W de Grip,
期刊:
Anti-Cancer Drugs
(OVID Available online 1994)
卷期:
Volume 5,
issue 1
页码: 35-42
ISSN:0959-4973
年代: 1994
出版商: OVID
关键词: Antineoplastic agents;combination index;median effect;protein synthesis inhibitors;sparsomycin
数据来源: OVID
摘要:
The modulating effect of ethyldeshydroxy-sparsomycin (EDSM), an inhibitor of ribosomal protein synthesis, on cytostatic agents was studied on cultured B16 melanoma cells using the microculture tetrazollum test (MTT). The data were analyzed for true synergism using the combination index and the median effect principle. The extent of cytotoxic drug interaction was influenced by the duration of drug exposure, the dose ratio, as well as the treatment schedule. When drug ratios were used, synergism was observed upon pre- and post-treatment in combination with cisplatin, cytosine arabinoside (Ara-C), methotrexate (MTX) and 5-fluorouracll (5-FU). The combination of a fixed dose of EDSM was synergistic with clsplatin, Ara-C, vincristine (VCR) and MTX, in the order MTX > Ara-C > VCR > cisplatin, while the combinations with doxorubicin, 5-FU and etoposide (VP-16) were shown to be antagonistic. These results suggest that only certain drugs and treatment schedules might be worthwhile for combination studies with EDSMIn vivoand indicate a role for EDSM as modifier of antitumor responses in cancer chemotherapy.
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