The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines
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The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines. / Güster, Julian David; Weissleder, Stephanie Valerie; Busch, Chia-Jung; Kriegs, Malte; Petersen, Cordula; Knecht, Rainald; Dikomey, Ekkehard; Rieckmann, Thorsten.
In: RADIOTHER ONCOL, Vol. 113, No. 3, 01.12.2014, p. 345-51.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines
AU - Güster, Julian David
AU - Weissleder, Stephanie Valerie
AU - Busch, Chia-Jung
AU - Kriegs, Malte
AU - Petersen, Cordula
AU - Knecht, Rainald
AU - Dikomey, Ekkehard
AU - Rieckmann, Thorsten
N1 - Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - BACKGROUND AND PURPOSE: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells.MATERIALS AND METHODS: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay.RESULTS: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1.CONCLUSIONS: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity.
AB - BACKGROUND AND PURPOSE: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells.MATERIALS AND METHODS: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay.RESULTS: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1.CONCLUSIONS: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity.
U2 - 10.1016/j.radonc.2014.10.011
DO - 10.1016/j.radonc.2014.10.011
M3 - SCORING: Journal article
C2 - 25467050
VL - 113
SP - 345
EP - 351
JO - RADIOTHER ONCOL
JF - RADIOTHER ONCOL
SN - 0167-8140
IS - 3
ER -