Enhancement of radiation effects by combined docetaxel and flavopiridol treatment in lung cancer cells

Jae Chul Kim, Debabrata Saha, Qianwen Cao, Hak Choy

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background and purpose To evaluate the potential role and mechanism of docetaxel plus flavopiridol in modulating radiosensitivity in vitro and in vivo. Patients and methods In vitro. H460 human lung carcinoma cells were treated with docetaxel (10nM for 1 h, at t=0h)→radiation (0-5Gy, at t=6h)→flavopiridol (120nM for 24 h, at t=8h). 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=0h)→radiation (2Gy, at t=6h)→flavopiridol (1.25 mg/kg, at t=8h) 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.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalRadiotherapy and Oncology
Volume71
Issue number2
DOIs
StatePublished - May 2004

Fingerprint

alvocidib
docetaxel
Radiation Effects
Lung Neoplasms
Therapeutics
Apoptosis
Cell Cycle
Radiation
Propidium
Radiation Tolerance

Keywords

  • Docetaxel
  • Flavopiridol
  • Radiosensitization

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Urology

Cite this

Enhancement of radiation effects by combined docetaxel and flavopiridol treatment in lung cancer cells. / Kim, Jae Chul; Saha, Debabrata; Cao, Qianwen; Choy, Hak.

In: Radiotherapy and Oncology, Vol. 71, No. 2, 05.2004, p. 213-221.

Research output: Contribution to journalArticle

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abstract = "Background and purpose To evaluate the potential role and mechanism of docetaxel plus flavopiridol in modulating radiosensitivity in vitro and in vivo. Patients and methods In vitro. H460 human lung carcinoma cells were treated with docetaxel (10nM for 1 h, at t=0h)→radiation (0-5Gy, at t=6h)→flavopiridol (120nM for 24 h, at t=8h). 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=0h)→radiation (2Gy, at t=6h)→flavopiridol (1.25 mg/kg, at t=8h) 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.",
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N2 - Background and purpose To evaluate the potential role and mechanism of docetaxel plus flavopiridol in modulating radiosensitivity in vitro and in vivo. Patients and methods In vitro. H460 human lung carcinoma cells were treated with docetaxel (10nM for 1 h, at t=0h)→radiation (0-5Gy, at t=6h)→flavopiridol (120nM for 24 h, at t=8h). 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=0h)→radiation (2Gy, at t=6h)→flavopiridol (1.25 mg/kg, at t=8h) 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.

AB - Background and purpose To evaluate the potential role and mechanism of docetaxel plus flavopiridol in modulating radiosensitivity in vitro and in vivo. Patients and methods In vitro. H460 human lung carcinoma cells were treated with docetaxel (10nM for 1 h, at t=0h)→radiation (0-5Gy, at t=6h)→flavopiridol (120nM for 24 h, at t=8h). 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=0h)→radiation (2Gy, at t=6h)→flavopiridol (1.25 mg/kg, at t=8h) 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.

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