Effect of ketoprofen in topical formulation on vascular endothelial growth factor expression and tumor growth in nude mice with osteosarcoma.
OST cells, a low metastatic cell line established from human osteosarcoma, were inoculated under the periosteum of the ossa cranii of nude mice. Four weeks later, tumors were percutaneously treated for an additional 4 weeks with a patch containing either placebo or ketoprofen (KP). In the placebo group, OST cells formed osteoid and invaded the cranial bone. Tumor mass weighed 3.54 g. Approximately 85% of cells within the tumor expressed proliferating cell nuclear antigen (PCNA), indicating that they were proliferating with a high mitotic activity. Many feeder vessels were located within the tumor. The majority of tumor cells expressed intensely vascular endothelial growth factor (VEGF). In the KP group, invasion of OST cells into the cranial bone was suppressed and the tumor mass was 47% of that of the placebo group. Approximately 65% of cells within the tumor were PCNA-negative, indicating that their growth was arrested. There were considerably fewer feeder vessels within the tumor in the KP group than in the placebo group. Only a small number of cells expressed VEGF. Based on these findings, we concluded that topical administration of KP to nude mice with osteosarcoma inhibited VEGF expression, reduced the development of feeder vessels for supply of nutrients and oxygen, and suppressed tumor growth.
Department of Orthopaedic Surgery, School of Medicine, Ehime University, Shigenobu, Onsen-gun, 791-0295, Japan. kenshi@m.ehime-u.ac.jp
Kenshi
K
Sakayama
Teruki
T
Kidani
Tatsuhiko
T
Miyazaki
Haruo
H
Shirakata
Yoshiyuki
Y
Kimura
Junji
J
Kamogawa
Hiroshi
H
Masuno
Haruyasu
H
Yamamoto
D000287:Administration, Topical; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D012516:Osteosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D012888:Skull Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D042461:Vascular Endothelial Growth Factor A; D007660:Ketoprofen; D000469:Alkaline Phosphatase