Flavopiridol as a radio-sensitizer for esophageal cancer cell lines.
Flavopiridol is a synthetic flavone that has shown an antitumor effect against several cancers. Here, we investigated the in vitro effect of flavopiridol alone and the combined effect of low-dose flavopiridol plus radiation on esophageal squamous cell carcinoma cell lines. Esophageal squamous cell carcinoma cell lines (TE8, TE9 and KE4) were exposed to flavopiridol (0.05-400 nmol/L) for 48 h. Growth inhibition was evaluated by MTT assay, cell cycle distribution was determined by flow cytometry, and cyclin D1, Bcl-2 and Rb protein expression was detected by Western blotting. The effect of 0.05 nmol/L flavopiridol as a radio-sensitizer was determined by clonogenic assay. The IC50 was approximately 110-250 nmol/L. Exposure to 0.05 nmol/L flavopiridol for 48 h increased the G2/M population, while 300 nmol/L increased the G1 population. At a concentration of 300 nmol/L, nuclear fragmentation and chromatin condensation were observed in all three cell lines. Exposure to 300 nmol/L flavopiridol decreased the levels of cyclin D1 and Rb protein in all three cell lines and Bcl-2 protein was also decreased in TE8 and KE4 cells. Moreover, exposure to 0.05 nmol/L flavopiridol slightly decreased the levels of cyclin D1, Rb and Bcl-2 protein in KE4 cells. Flavopiridol treatment (0.05 nmol/L) enhanced the radio-sensitivity in all three cell lines. Low-dose flavopiridol augmented the response of esophageal squamous cell carcinoma cell lines to radiation. Administration of a low dose of flavopiridol could be a potent new therapeutic approach for improving the efficacy of radiotherapy against esophageal cancer.
Sato
S
S
First Department of Surgery, Juntendo University School of Medicine, Tokyo, Japan. ssato@maz.miinet.or.jp
Kajiyama
Y
Y
Sugano
M
M
Iwanuma
Y
Y
Tsurumaru
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D019938:Cyclin D1 / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D005562:Formazans; D019254:Genes, bcl-2 / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000187:drug effects; D013778:Tetrazolium Salts; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005419:Flavonoids; D005562:Formazans; D006131:Growth Inhibitors; D010880:Piperidines; D011838:Radiation-Sensitizing Agents; D016160:Retinoblastoma Protein; D013778:Tetrazolium Salts; D019938:Cyclin D1; C079782:MTT formazan; C077990:alvocidib