Differential antiproliferative activities of alpha- and gamma-interferon and tumor necrosis factor alone or in combinations against two prostate cancer xenografts transplanted in nude mice.
We have investigated the antiproliferative effects of recombinant human alpha- and gamma-Interferon (IFN) and recombinant human Tumor Necrosis Factor alpha (TNF) against the hormone-independently growing PC3 and DU145 prostatic tumor lines. Subcutaneous, peritumoral administration of the drugs was started 24 hours after subcutaneous implantation of 1-2 mm3 tumor pieces. IFN was given three times per week and TNF five times per week. IFN-alpha (dose-range 0.5-5 ng/gram bodyweight) had significant growth-inhibiting effects against the PC3 tumor, but showed no significant antitumor effects against the DU145 tumor. IFN-gamma monotherapy (dose-range 8-80 ng/gram bodyweight) was less effective than IFN-alpha. 500 ng/gram TNF produced growth inhibition of both tumors, whereas the lower dose (50 ng/g) was only effective against the PC3 tumor. IFN-alpha and -gamma combination treatment had significant antiproliferative effects against the PC3 tumor, but not against the DU145 tumor. Combinations of IFN-alpha and TNF were very effective against both xenografts; some combinations resulted in complete growth inhibition. IFN-gamma and TNF combinations also showed significant antitumor effects against both tumor lines. We therefore conclude that cytokine combination treatment may provide a new approach in the treatment of hormone-escaped prostatic tumors.
van Moorselaar
R J
RJ
Department of Urology, University Hospital Nijmegen, The Netherlands.
van Stratum
P
P
Borm
G
G
Debruyne
F M
FM
Schalken
J A
JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007370:Interferon Type I / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins; D012044:Regression Analysis; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma