Premium
Head and neck cancer radiosensitization by the novel poly(ADP‐ribose) polymerase inhibitor GPI‐15427
Author(s) -
Khan Khurram,
Araki Koji,
Wang Daiyou,
Li Guayan,
Li Xin,
Zhang Jie,
Xu Weizheng,
Hoover Randall K.,
Lauter Susan,
O'Malley Bert,
Lapidus Rena G.,
Li Daqing
Publication year - 2010
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.21195
Subject(s) - in vivo , apoptosis , poly adp ribose polymerase , head and neck cancer , cancer research , in vitro , head and neck squamous cell carcinoma , radiation therapy , parp inhibitor , dna damage , cancer , comet assay , chemistry , microbiology and biotechnology , polymerase , medicine , biology , dna , biochemistry
Abstract Background In this study, we tested the ability of a novel poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, 10‐(4‐methyl‐piperazin‐1‐ylmethyl)‐2 H ‐7‐oxa‐1,2‐diaza‐benzo[ de ]‐anthracen‐3‐one (GPI‐15427), to enhance the effect of radiotherapy in a xenograft model of human head and neck squamous cell carcinoma (HNSCC). Methods Human xenograft HNSCC tumors were established in female nude mice: animals were treated with orally administered GPI‐15427 at varied doses prior to tumor irradiation. In vitro and in vivo apoptosis analyses and neutral single‐cell gel electrophoresis (comet) assay were performed, with the “tail moment” calculated to evaluate DNA double‐strand break damage. Results Orally administered GPI‐15427 given before radiation therapy significantly reduced tumor volume, and cells demonstrated significantly elevated mean tail moments (indicative of DNA damage) and enhanced apoptosis both in vitro and in vivo, compared with radiation‐alone and control groups. Conclusions Use of the PARP‐1 inhibitor GPI‐15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010