Abstract
The effect of sequential methotrexate and 5-fluorouracil on the clonal growth of the human colon adenocarcinoma cell, HCT-8, and the hormone-dependent human breast carcinoma cell, 47-DN, was examined. In both cell lines, when 5-fluorouracil was given during the last 6 h of a 24 h methotrexate exposure period, there was marked synergistic inhibition of clonal growth. Shorter intervals or the reverse sequence of drugs were either additive or antagonistic. These results indicate the importance of the drug sequence and time interval between drug administration for optimal cytotoxicity in these human cell lines. This information suggests that the administration of methotrexate 18 h before 5-fluorouracil may have potential application in the design of clinical trials for these malignancies.
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- Bertino J. R., Sawicki W. L., Lindquist C. A., Gupta V. S. Schedule-dependent antitumor effects of methotrexate and 5-fluorouracil. Cancer Res. 1977 Jan;37(1):327–328. [PubMed] [Google Scholar]
- Cadman E., Heimer R., Davis L. Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism. Science. 1979 Sep 14;205(4411):1135–1137. doi: 10.1126/science.472732. [DOI] [PubMed] [Google Scholar]
- Carrico C. K., Glazer R. I. Effect of 5-fluorouracil on the synthesis and translation of polyadenylic acid-containing RNA from regenerating rat liver. Cancer Res. 1979 Sep;39(9):3694–3701. [PubMed] [Google Scholar]
- Hamburger A. W., Salmon S. E. Primary bioassay of human tumor stem cells. Science. 1977 Jul 29;197(4302):461–463. doi: 10.1126/science.560061. [DOI] [PubMed] [Google Scholar]
- Harrap K. R., Jackson R. C. Enzyme kinetics and combination chemotherapy: an appraisal of current concepts. Adv Enzyme Regul. 1975;13:77–96. doi: 10.1016/0065-2571(75)90009-6. [DOI] [PubMed] [Google Scholar]
- Keydar I., Chen L., Karby S., Weiss F. R., Delarea J., Radu M., Chaitcik S., Brenner H. J. Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer. 1979 May;15(5):659–670. doi: 10.1016/0014-2964(79)90139-7. [DOI] [PubMed] [Google Scholar]
- Reyes P., Guganig M. E. Studies on a pyrimidine phosphoribosyltransferase from murine leukemia P1534J. Partial purification, substrate specificity, and evidence for its existence as a bifunctional complex with orotidine 5-phosphate decarboxylase. J Biol Chem. 1975 Jul 10;250(13):5097–5108. [PubMed] [Google Scholar]
- Tompkins W. A., Watrach A. M., Schmale J. D., Schultz R. M., Harris J. A. Cultural and antigenic properties of newly established cell strains derived from adenocarcinomas of the human colon and rectum. J Natl Cancer Inst. 1974 Apr;52(4):1101–1110. doi: 10.1093/jnci/52.4.1101. [DOI] [PubMed] [Google Scholar]
- Ullman B., Lee M., Martin D. W., Jr, Santi D. V. Cytotoxicity of 5-fluoro-2'-deoxyuridine: requirement for reduced folate cofactors and antagonism by methotrexate. Proc Natl Acad Sci U S A. 1978 Feb;75(2):980–983. doi: 10.1073/pnas.75.2.980. [DOI] [PMC free article] [PubMed] [Google Scholar]