Therapeutic efficacy of recombinant tumor necrosis factor alpha in an experimental model of human prostatic carcinoma.
Prostatic carcinoma represents the second leading cause of cancer mortality in men and is responsible for over 25,000 deaths each year. Currently, no curative therapy is available for metastatic carcinoma of the prostate. The present studies were undertaken to assess the efficacy of recombinant tumor necrosis factor alpha (TNF) in the therapy of experimental prostatic carcinoma. TNF was cytotoxic to the prostate cancer cell lines PC3, DU145, and LNCAP but not benign prostatic epithelial and stromal cells in vitro. The sensitivity of the prostatic carcinoma lines to TNF-mediated cytotoxicity was enhanced by the presence of actinomycin D. Intravenous administration of TNF (50-100 micrograms/kg) to nude mice bearing subcutaneous PC3 tumors resulted in significant inhibition of primary tumor growth compared to control. TNF was also effective in reducing the growth of intraabdominal PC3 tumors induced by intrasplenic injection of PC3. Furthermore, the incidence of microscopic PC3 foci in the spleen, liver, lung, and diaphragm was diminished in mice receiving TNF therapy. These studies demonstrate the potential of TNF in the therapy of human prostatic carcinoma.
Sherwood
E R
ER
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611.
Pitt Ford
T R
TR
Lee
C
C
Kozlowski
J M
JM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha