Anti-angiogenic effects of Hypericin-photodynamic therapy in combination with Celebrex in the treatment of human nasopharyngeal carcinoma.
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.
Yee
Karen Kar Lye
KK
National Cancer Centre Singapore, Singapore 169610.
Soo
Khee Chee
KC
Olivo
Malini
M
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
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