Schedule dependent potentiation of antitumor drug effects by alpha-difluoromethylornithine in human gastric carcinoma cells in vitro

• Published in: Investigational new drugs 1990-03, Vol.8 Suppl 1 (S1), p.S9-S18
• Main Authors: Barranco, S C, Townsend, Jr, C M, Ho, B Y, Reumont, K J, Koester, S K, Ford, P J
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Bleomycin - administration & dosage; Bleomycin - therapeutic use; Cell Cycle - drug effects; Cell Survival - drug effects; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Drug Administration Schedule; Drug Therapy, Combination; Eflornithine - administration & dosage; Eflornithine - pharmacology; Fluorouracil - administration & dosage; Fluorouracil - therapeutic use; Humans; Ornithine Decarboxylase - metabolism; Polyamines - metabolism; Semustine - administration & dosage; Semustine - therapeutic use; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Time Factors; Tumor Cells, Cultured - drug effects
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/BF00171979

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with alpha-difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.