title: Anti-angiogenic effects of Hypericin-photodynamic therapy in combination with Celebrex in the treatment of human nasopharyngeal carcinoma.
abstract: Photodynamic therapy (PDT) is being investigated as an alternative treatment modality in cancer treatment. It has been shown to induce tumor hypoxia and upregulation of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). The objective of this study was to improve in vivo tumor growth control of nasopharyngeal carcinoma (NPC), treated at a subcurative dosage by using a combination of Hypericin-PDT and COX-2 inhibitor, Celebrex (CX). The effect of an initial CX dose at 6- and 24-h post-PDT was investigated simultaneously. It was observed that hypoxic NPC/CNE2 cells upregulate both COX-2 and VEGF A genes in vitro. In vivo studies, down-regulation of COX-2 and hypoxia inducible factor-1alpha (HIF-1alpha) genes at 24-h post-PDT and bulk tumor ablation at 48-h post-PDT was observed. However, 24-28 days later regrowth was observed. In a combination treatment, 1st CX dose at 6-h post-PDT had the highest tumor control in which tumors were <or=0.52 cm(3) (64.29%, P<0.05). However, the tumors administered with a initial dose of CX at 24-h post-PDT had no tumor control. Co-suppression of COX-2, HIF-1alpha and VEGF A genes were observed in tumors with tumor control. Mice without tumor control that were subjected to therapy had increased human VEGF in serum compared to Hypericin-PDT mice. Thus, suggesting that the time of initial administration of CX post-PDT is an important factor for effective tumor control.
authors.affiliation: National Cancer Centre Singapore, Singapore 169610.
authors.forename: Karen Kar Lye
authors.initials: KK
authors.lastname: Yee
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000873:Anthracenes; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004359:Drug Therapy, Combination; D005070:Evans Blue; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009336:Necrosis / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D010778:Photochemotherapy; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D005070:Evans Blue; D010569:Perylene; C004965:hypericin; D051546:Cyclooxygenase 2; D000068579:Celecoxib