Enhancement of radiation effects by combined docetaxel and flavopiridol treatment in lung cancer cells.
OBJECTIVE
To evaluate the potential role and mechanism of docetaxel plus flavopiridol in modulating radiosensitivity in vitro and in vivo.


METHODS
In vitro. H460 human lung carcinoma cells were treated with docetaxel (10 nM for 1 h, at t = 0 h) --> radiation (0-5 Gy, at t = 6 h) --> flavopiridol (120 nM for 24 h, at t = 8 h). Colony forming ability was measured to assess the modulation of sensitivity. Cell cycle redistribution was measured by flow cytometric analysis using propidium iodide. Percent apoptosis was also measured by flow cytometric analysis using 7-amino-actinomycin D staining. In vivo. H460 cell xenografts were used in nude mice. Tumors were grown subcutaneously on the flank, then treated with docetaxel (2.5 mg/kg, at t = 0 h) --> radiation (2 Gy, at t = 6 h) --> flavopiridol (1.25 mg/kg, at t = 8 h) for 5 consecutive days. Tumor growth delay was then measured and compared with the control group.


RESULTS
Docetaxel plus flavopiridol enhanced the effect of radiation. The maximum radiopotentiation and apoptosis were observed when the cells were treated with the sequence of docetaxel-->radiation-->flavopiridol both in vitro and in vivo. Flavopiridol and docetaxel induced G1 and G2/M arrest, respectively.


CONCLUSIONS
This study shows that docetaxel plus flavopiridol enhances the effects of radiation in vitro and in vivo. Our data suggest that the mechanism of radiopotentiation by combining flavopiridol and docetaxel involves an enhancement of apoptosis and changes of cell cycle by docetaxel and flavopiridol.
Kim
Jae-Chul
JC
Moncrief Radiation Oncology center, University of Texas Southwestern Medical Center; 5801 Forest Park Road, Dallas, TX 75390-9183, USA.
Saha
Debabrata
D
Cao
Qianwen
Q
Choy
Hak
H
D000818:Animals; D002470:Cell Survival; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000494:pharmacology*; D011336:Probability; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D015996:Survival Rate; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*; D023041:Xenograft Model Antitumor Assays
D005419:Flavonoids; D010880:Piperidines; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; C077990:alvocidib