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Clin Cancer Res. 2003 Apr;9(4):1557-65.

Low-dose fractionated radiation potentiates the effects of Paclitaxel in wild-type and mutant p53 head and neck tumor cell lines.

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Department of Radiation Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.


This study was designed to: (a) evaluate the induction of hyper-radiation sensitivity (HRS), a phenomenon observed at low doses of radiation (<1 Gy); (b) compare the potentiating effects of single dose radiation (2 Gy) versus the effect of low-dose fractionated radiation (LDFRT; <1 Gy) on Paclitaxel; and (c) understand the molecular mechanism of LDFRT-mediated chemo-potentiating effects, in wild-type p53 SCC-61 and p53 mutant SQ-20B head and neck squamous cell carcinoma cell lines. Both cell lines exhibited the HRS phenomenon at low radiation doses. Compared with SCC-61 cells, SQ-20B cells were resistant to radiation and Paclitaxel alone. A significant enhancement of radiation sensitization by Paclitaxel (0.5 or 1 nM) was observed in both cell lines. Chemo-potentiation of Paclitaxel by single 2-Gy radiation was observed in SCC-61 cells but not in SQ-20B cells. However, LDFRT (0.5 Gy in four fractions) significantly chemo-potentiated the effect of Paclitaxel in both cell lines. The cell cycle regulator p53 and its target genes p21(waf1/cip1) and BAX were induced in SCC-61 cells treated with 2 Gy, Paclitaxel, or in combination, but not in SQ-20B cells. These treatments elevated the antiapoptotic BCL-2 protein in SQ-20B cells but not in SCC-61 cells. Interestingly, LDFRT treatment in both cell lines with or without Paclitaxel down-regulated nuclear factor kappa B activity and BCL-2 protein expression and simultaneously up-regulated BAX protein. These findings strongly suggest that LDFRT (at these doses, HRS phenomenon is observed) can be used in combination with Paclitaxel to overcome the antiapoptotic effects of BCL-2 and nuclear factor kappa B.

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