title: Expression of vascular endothelial growth factor by photodynamic therapy with mono-L-aspartyl chlorin e6 (NPe6) in oral squamous cell carcinoma.
abstract: Photodynamic therapy (PDT) is a method for treating pre-cancerous and cancerous lesions of the skin, bladder and oral cavity. However, tumour recurrence after PDT remains problematic despite good initial response. Some studies have shown that PDT induces vascular endothelial growth factor (VEGF) expression in human oral squamous cell carcinoma and other organs. However, little is known about VEGF expression applied to PDT in human carcinoma cell lines. No studies have been conducted of PDT using Npe6 (Npe6-mediated PDT), a second-generation photosensitizer, in the human oral carcinoma cell line, HSC-3 cells. We investigated the expression of VEGF, c-jun and c-fos proto-oncogenes in HSC-3 cells in response to Npe6-mediated PDT. We also addressed the possibility that oxidative damage induced by PDT could lead to an angiogenic response, via VEGF expression. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that Npe6-mediated PDT induced the expression of mRNAs for VEGF, c-jun and c-fos in time- and concentration-dependent manners. Desferrioxamine (DFX), an iron chelator, induced VEGF expression, but the expression pattern was different to that of Npe6-mediated PDT. The expression mRNAs for VEGF, c-jun and c-fos induced by Npe6-mediated PDT were inhibited by SB203580, p38 MAPK inhibitors, and the expression of VEGF mRNA was inhibited by cycloheximide (CHX), a protein synthesis inhibitor. The c-jun mRNA expression was inhibited, whereas the c-fos mRNA expression was enhanced by N-acetyl-L-cysteine (NAC), a free radical scavenger. We conclude that Npe6-mediated PDT induces the expression of VEGF, c-jun and c-fos in human oral carcinoma cell line, HSC-3 cell, and at least partly, through the activation of p38 MAPK.
authors.affiliation: Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine, Hirosaki, Japan. hnaka@vega.ocn.ne.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakaki
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kousei
authors.initials: K
authors.lastname: Kubota
authors.forename: Akinori
authors.initials: A
authors.lastname: Kusumi
authors.forename: Wataru
authors.initials: W
authors.lastname: Kobayashi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kimura
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017262:Siderophores / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007093:Imidazoles; D017319:Photosensitizing Agents; D011166:Porphyrins; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D017262:Siderophores; D042461:Vascular Endothelial Growth Factor A; D003513:Cycloheximide; D048051:p38 Mitogen-Activated Protein Kinases; D003676:Deferoxamine; C093642:SB 203580; C053434:Talaporfin