Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis.
The ability to metastasize requires that tumor cells be able to degrade matrix. Nontoxic compounds that inhibit matrix digestion might be useful as anti-metastatic agents. We have investigated whether phenytoin, a drug commonly used in clinical practice that inhibits the production of collagenase by some cells, inhibits metastases in a standard animal model of metastasis: In vitro, phenytoin inhibited the proliferative response of B16 F10 melanoma cells to serum-containing media (75% inhibition at 25 micrograms/ml) but had no effect on their ability to degrade a type I collagen gel (1-100 micrograms/ml). Treatment of these cells with phenytoin prior to inoculation in vivo did not inhibit tumor growth, implantation in a surgical wound, or incidence of spontaneous metastases from a primary tumor growing in the foot. Pretreatment of mice with phenytoin (15, 40, and 75 mg/kg/day) diminished pulmonary metastases following tail vein injection in a minimal but dose dependent fashion; mean number of pulmonary colonies 4.6 +/- 3.1 (75/mg/kg/day) vs. 10.2 +/- 9.9 (control). However, tumor growth, implantation, and spontaneous metastases were not inhibited by pretreating the mice with the same doses of phenytoin. It is concluded that phenytoin has an insignificant inhibitory effect on tumor growth and metastasis.
Dyce
M
M
Department of Surgery, Cornell University Medical College, New York, New York.
Sharif
S F
SF
Whalen
G F
GF
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D010672:Phenytoin / Q000494:pharmacology*
D010672:Phenytoin