15-deoxyprostaglandin-j2 and Stomach-Neoplasms

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been shown to inhibit angiogenesis. We showed that treatment with 15d-PGJ(2), a PPARgamma ligand, downregulate the expressions of angiopoietin-1 (Ang-1) in gastric cancer cells MKN45. The medium of MKN45 cells treated with 15d-PGJ(2) significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, Matrigel plug assay revealed that 15d-PGJ(2) reduced in vivo angiogenesis induced by MKN45 cells. These modulations were restored by the addition of recombinant Ang-1. Our findings supported that 15d-PGJ(2) suppressed angiogenesis of gastric cancer cells by downregulation of Ang-1.

Topics: Angiogenesis Inhibitors; Angiopoietin-1; Animals; Cell Line; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Down-Regulation; Endothelial Cells; Female; Gene Expression Profiling; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Neovascularization, Physiologic; Oligonucleotide Array Sequence Analysis; Prostaglandin D2; Stomach Neoplasms; Vascular Endothelial Growth Factor A

To investigate the influence of peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, 15-deoxy-12, 14-prostaglandin J2 (15dPGJ2) on the proliferation and apoptosis of MCG-803 human gastric cancer cell lines.. Cell proliferation was measured by 3H-TdR assay. Apoptosis was determined by ELISA and TUNEL staining. Protein and mRNA level of bcl-2 family and COXs were measured by Western blotting and Northern blotting respectively. PGE2 production was examined by RIA.. 15dPGJ2 inhibited cell growth and induced apoptosis of MCG-803 cells. The COX-2 and bcl-2/bax ratios were decreased following 15dPGJ2 treatment. The PGE2 production in supernatants was also decreased. These changes were in a dose-dependent manner.. 15dPGJ2 may be a useful therapeutic agent for the treatment of gastric cancer.

Topics: Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Cell Division; Cell Line, Tumor; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Membrane Proteins; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Stomach Neoplasms; Transcription Factors