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Radiother Oncol. 2003 Sep;68(3):305-13.

Potential radiation-sensitizing effect of semisynthetic epothilone B in human lung cancer cells.

Author information

1
Department of Radiation Oncology, The Vanderbilt Clinic B-902, 1003 TVC Vanderbilt University Medical Center, 1301 22nd Avenue South, Nashville, TN 37232-5671, USA.

Abstract

BACKGROUND AND PURPOSE:

To evaluate a semisynthetic epothilone B, BMS-247550, as a potential radiosensitizer in vitro and in vivo.

MATERIALS AND METHODS:

Human NCI-H460 lung cancer cells were treated with either BMS-247550 or paclitaxel and in combination with radiation at multiple doses for different time periods. Surviving fractions were then analyzed using a clonogenic assay. Cell cycle redistribution by BMS-247550 was measured with propidium iodide and flow cytometry. Percent apoptosis was also measured using 7-amino-actinomycin D staining with flow cytometry. For in vivo studies, the H460 xenograft model was used in athymic nude mice. Tumors were treated with BMS-247550 (5 mg/kg) i.p. injection on days 0, 2, and 4 and/or radiation (2 Gy/day, days 0-4).

RESULTS:

The in vitro radiation dose enhancement ratios (DER) of 1-h BMS-247550 and paclitaxel were 2.03 and 1.34, respectively. Treatment with BMS-247550 enhanced the G2/M block and induced apoptosis; whereas in combination with radiation, the induction of apoptosis was additive. BMS-247550 in combination with radiation in vivo enhanced the tumor growth delay when compared with either drug or radiation alone.

CONCLUSIONS:

These results demonstrated that BMS-247550 could enhance the effects of radiation in human lung cancer cells both in vitro and in vivo and that a G2/M block and increased apoptosis might be possible explanations for the enhancement.

PMID:
13129641
[Indexed for MEDLINE]

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