Abstract | BACKGROUND: 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.
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Authors | Khurram Khan, Koji Araki, Daiyou Wang, Guayan Li, Xin Li, Jie Zhang, Weizheng Xu, Randall K Hoover, Susan Lauter, Bert O'Malley Jr, Rena G Lapidus, Daqing Li |
Journal | Head & neck
(Head Neck)
Vol. 32
Issue 3
Pg. 381-91
(Mar 2010)
ISSN: 1097-0347 [Electronic] United States |
PMID | 19672867
(Publication Type: Journal Article)
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Chemical References |
- Organic Chemicals
- Poly(ADP-ribose) Polymerase Inhibitors
- Radiation-Sensitizing Agents
- GPI 15427
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Topics |
- Administration, Oral
- Animals
- Apoptosis
(drug effects)
- Carcinoma, Squamous Cell
(metabolism, pathology, radiotherapy)
- Comet Assay
- Female
- Head and Neck Neoplasms
(metabolism, pathology, radiotherapy)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Organic Chemicals
(administration & dosage, pharmacokinetics, therapeutic use)
- Poly(ADP-ribose) Polymerase Inhibitors
- Radiation-Sensitizing Agents
(administration & dosage, pharmacokinetics, therapeutic use)
- Xenograft Model Antitumor Assays
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