All-trans retinoic acid inhibits the cell proliferation but enhances the cell invasion through up-regulation of c-met in pancreatic cancer cells.
All-trans retinoic acid (ATRA) inhibits proliferation of cancer. However, the effects of ATRA on scattering and invasion of pancreatic cancer cells remain unknown. Also, the effects of ATRA on c-Met expression in pancreatic cancer have never been addressed so far. The effects of ATRA on a pancreatic cancer cell line, Capan-1, were determined by proliferation assay, scattering assay and invasion assay. In addition, the expression of c-Met in pancreatic cancer cell lines treated with ATRA was investigated by real-time PCR and western blotting. The growth-inhibitory effect of ATRA was found when the cells were cultured with 5 microM ATRA for 3 days. In cell scattering assay, ATRA-treated pancreatic cancer cells were found to spread out from their colonies. In invasion assay, cells treated with ATRA invaded the matrigel more than vehicle-treated cells. The expression of c-Met was up-regulated both in the mRNA and protein levels after the treatment of ATRA. The highest expression was found at 48 h after the treatment. ATRA induced scattering and invasion of pancreatic cancer cells, although it inhibited proliferation of those cells. In addition, ATRA also increased the protein level of c-Met. These findings may indicate that the use of retinoic acid as an anti-cancer therapeutic drug needs some additional treatments to control cell invasion or scattering.
Leelawat
Kawin
K
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan; Department of Surgery, Rajavithi Hospital, Bangkok, Thailand.
Ohuchida
Kenoki
K
Mizumoto
Kazuhiro
K
Mahidol
Chulabhorn
C
Tanaka
Masao
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D014212:Tretinoin; D019859:Proto-Oncogene Proteins c-met