Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis.
Alvocidib (Flavopiridol, HMR1275) is a potent inhibitor of multiple cyclin-dependent kinases and has been identified recently as an antitumor agent in several cancers. Previous studies have shown that alvocidib could potentially treat esophageal cancer in vitro. This study evaluates alvocidib for its ability to suppress tumor growth in severe combined immunodeficiency (SCID) mice bearing TE8 human esophageal squamous cell carcinoma (SCC) xenografts. Alvocidib treatment of 10mg/kg body weight reduced tumor volume significantly. Immunohistochemistry analysis of alvocidib-treated tumor sections showed significant reductions in cyclin D1, VEGF, and Rb levels. Alvocidib treatment did not cause a marked increase in apoptotic tumor cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis, yet hematoxylin and eosin staining revealed tumor necrosis. In vivo investigation of alvocidib treatment confirmed antitumor activity in TE8 esophageal xenografts. These findings suggest that alvocidib could be a useful anti-cancer agent for esophageal cancer.
Sato
Shinsuke
S
Department of Gastroenterological Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. ssato@maz.miinet.or.jp
Kajiyama
Yoshiaki
Y
Sugano
Masahiko
M
Iwanuma
Yoshimi
Y
Sonoue
Hiroshi
H
Matsumoto
Toshiharu
T
Tsurumaru
Masahiko
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D016513:Mice, SCID; D009336:Necrosis; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; D016160:Retinoblastoma Protein; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; C077990:alvocidib