In vitro antiproliferative efficacy of interferon-alpha, -gamma and tumor necrosis factor on two human renal tumor xenografts.
The in vitro antitumor activity of recombinant alpha- and gamma-Interferon as well as recombinant Tumor Necrosis Factor alpha was tested on renal cell carcinoma xenografts using the double layer soft agar method. Using this assay, the effect of the drugs on the clonogenic potential of tumor cells in soft agar was determined and used as an indication for the antiproliferative capacity of these drugs. There appeared to be a differential response of the tested xenografts towards these drugs in a dose dependent way. However, when used in combination in most cases an additive or synergistic effect was observed. Even though again the response was differential, the combination of alpha-Interferon (10 ng/dish) and Tumor Necrosis Factor (100 ng/dish) resulted in a complete inhibition of colony formation in soft agar for both tumor lines. We conclude that there is a direct effect of alpha-Interferon, gamma-Interferon and Tumor Necrosis Factor on renal cell carcinoma xenografts. In combination drug tests the effect of alpha-Interferon and Tumor Necrosis Factor was strongly synergistic. The implication of these studies for in vivo use of these drugs remain to be established.
Beniers
A J
AJ
Department of Urology, St. Radboud University Hospital, Nijmegen, The Netherlands.
Peelen
W P
WP
Hendriks
B T
BT
Schalken
J A
JA
Romijn
J C
JC
Debruyne
F M
FM
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D004357:Drug Synergism; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D014410:Tumor Stem Cell Assay
D014409:Tumor Necrosis Factor-alpha; D007372:Interferons