Augmentation of antiproliferative activity of recombinant human tumor necrosis factor by delta 12-prostaglandin J2.
The effects of tumor necrosis factor (TNF) and cyclopentenone prostaglandins (PGA2 and delta 12-PGJ2), singly and in combination, against proliferation in three human gynecologic tumor cell lines (HeLa S3, HHUA, and CAOV-3) were examined in vitro. The HeLa S3 and CAOV-3 cells were unresponsive to TNF, and the HHUA cells exhibited a minimal degree of responsiveness to TNF. The HeLa S3 and HHUA cells were responsive dose-dependently to PGA2, and the CAOV-3 cells were slightly responsive to PGA2. All three cell lines were highly responsive to delta 12-PGJ2. The synergistic antiproliferative effect of TNF and delta 12-PGJ2 appeared in all three cell lines. Pretreatment with delta 12-PGJ2 enhanced the effectiveness of TNF in these cell lines, but not vice versa. A synergistic interaction between TNF and PGA2 was absent in these three cell lines. These results suggest that a combined treatment with TNF and delta 12-PGJ2 could provide a new approach to obtaining increased responses in clinical trials.
Mori
H
H
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Takada
Y
Y
Kondoh
H
H
Tamaya
T
T
D000971:Antineoplastic Combined Chemotherapy Protocols; D002455:Cell Division; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000627:therapeutic use / Q000031:analogs & derivatives; D011454:Prostaglandins A / Q000008:administration & dosage / Q000627:therapeutic use*; D011465:Prostaglandins, Synthetic; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
D011454:Prostaglandins A; D011465:Prostaglandins, Synthetic; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; C100008:prostaglandin A2; D015230:Prostaglandin D2