Loxoprofen sodium suppresses mouse tumor growth by inhibiting vascular endothelial growth factor.
There is increasing evidence to suggest the anti-tumor effects of non-steroidal anti-inflammatory drugs (NSAIDs). In this study it was shown that the most popular NSAID in Japan, loxoprofen sodium (LOX), inhibited in vivo growth of implanted Lewis lung carcinoma (LLC), whereas LOX did not affect the proliferation and viability of LLC cells in vitro. Intratumoral vessel density in LOX-treated mice was significantly lower than that of mice without treatment. Intratumoral expressions of vascular endothelial growth factor (VEGF) mRNA were attenuated by the LOX treatment. LOX suppressed both intratumoral and systemic VEGF protein in LLC-implanted mice. LOX also inhibited tubular formation of primary cultured human umbilical vein endothelial cells, presumably due to the inhibition of VEGF. In patients with advanced non-small cell lung cancer, LOX medication (120 mg/day) for a week significantly decreased the plasma VEGF level. These results suggest that LOX may have potent anti-cancer effects in patients with advanced NSCLC.
Kanda
Akio
A
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ebihara
Satoru
S
Takahashi
Hidenori
H
Sasaki
Hidetada
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000032:analysis / Q000037:antagonists & inhibitors*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008222:Lymphokines / Q000032:analysis / Q000037:antagonists & inhibitors*; D051379:Mice; D010666:Phenylpropionates / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010666:Phenylpropionates; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C040656:loxoprofen