Augmentation of antiproliferative activity of recombinant human tumor necrosis factor by delta 12-prostaglandin J2.

Abstract

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.