Elisabeth Foki1, Isabella Stanisz1, Lorenz Kadletz1, Ulana Kotowski1, Rudolf Seemann2, Rainer Schmid3, Gregor Heiduschka4. 1. Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. 2. Department of Oral and Maxillofacial surgery, Medical University of Vienna, Vienna, Austria. 3. Department of Radiotherapy, Medical University of Vienna, Vienna, Austria. 4. Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. gregor.heiduschka@meduniwien.ac.at.
Abstract
BACKGROUND: The selective PI3K (Phosphatidylinositol 3-kinase) inhibitor HS-173 has anticancer activity in non-small cell lung cancer and pancreatic cancer cells. Of all head and neck squamous cell carcinomas (HNSCC) 20% harbor specific mutations in the genome. The aim of this study was to investigate the effect of HS-173 on HNSCC cell lines. METHODS: The cell lines SCC25, CAL27 and FaDu were incubated with HS-173. Its antiproliferative effect was determined using the CCK‑8 cell proliferation assay. Combined incubation with cisplatin was performed and combination index analysis was conducted. To investigate its effect on radiotherapy, cells were irradiated with 2, 4, 6 and 8 Gy, respectively. Synergistic effects of radiation and HS-173 were measured by proliferation assays and clonogenic survival. RESULTS: The use of HS-173 induced significant reduction of cell proliferation across all cell lines. Most interestingly, it showed a synergistic effect with cisplatin treatment. Clonogenic survival revealed a radiosensitizing effect in CAL27 and FaDu cells. The HS-173 caused significant induction of apoptosis in SCC25 and FaDu cells. CONCLUSION: The selective PI3K inhibitor HS-173 is a potent chemosensitizing and also radiosensitizing drug in treatment of HNSCC cell lines and could be an effective treatment in PI3K-mutated HNSCC.
BACKGROUND: The selective PI3K (Phosphatidylinositol 3-kinase) inhibitor HS-173 has anticancer activity in non-small cell lung cancer and pancreatic cancer cells. Of all head and neck squamous cell carcinomas (HNSCC) 20% harbor specific mutations in the genome. The aim of this study was to investigate the effect of HS-173 on HNSCC cell lines. METHODS: The cell lines SCC25, CAL27 and FaDu were incubated with HS-173. Its antiproliferative effect was determined using the CCK‑8 cell proliferation assay. Combined incubation with cisplatin was performed and combination index analysis was conducted. To investigate its effect on radiotherapy, cells were irradiated with 2, 4, 6 and 8 Gy, respectively. Synergistic effects of radiation and HS-173 were measured by proliferation assays and clonogenic survival. RESULTS: The use of HS-173 induced significant reduction of cell proliferation across all cell lines. Most interestingly, it showed a synergistic effect with cisplatin treatment. Clonogenic survival revealed a radiosensitizing effect in CAL27 and FaDu cells. The HS-173 caused significant induction of apoptosis in SCC25 and FaDu cells. CONCLUSION: The selective PI3K inhibitor HS-173 is a potent chemosensitizing and also radiosensitizing drug in treatment of HNSCC cell lines and could be an effective treatment in PI3K-mutated HNSCC.
Entities:
Keywords:
Cell death; Chemosensitizer; Head and neck cancer; Radiosensitizer; Receptor tyrosine kinases
Authors: Christian Freudlsperger; Jeffrey R Burnett; Jay A Friedman; Vishnu R Kannabiran; Zhong Chen; Carter Van Waes Journal: Expert Opin Ther Targets Date: 2010-11-26 Impact factor: 6.902
Authors: Vivian W Y Lui; Matthew L Hedberg; Hua Li; Bhavana S Vangara; Kelsey Pendleton; Yan Zeng; Yiling Lu; Qiuhong Zhang; Yu Du; Breean R Gilbert; Maria Freilino; Sam Sauerwein; Noah D Peyser; Dong Xiao; Brenda Diergaarde; Lin Wang; Simion Chiosea; Raja Seethala; Jonas T Johnson; Seungwon Kim; Umamaheswar Duvvuri; Robert L Ferris; Marjorie Romkes; Tomoko Nukui; Patrick Kwok-Shing Ng; Levi A Garraway; Peter S Hammerman; Gordon B Mills; Jennifer R Grandis Journal: Cancer Discov Date: 2013-04-25 Impact factor: 39.397
Authors: Francesco Perri; Roberto Pacelli; Giuseppina Della Vittoria Scarpati; Laura Cella; Mario Giuliano; Francesco Caponigro; Stefano Pepe Journal: Head Neck Date: 2015-01-27 Impact factor: 3.147
Authors: Tanguy Y Seiwert; Zhixiang Zuo; Michaela K Keck; Arun Khattri; Chandra S Pedamallu; Thomas Stricker; Christopher Brown; Trevor J Pugh; Petar Stojanov; Juok Cho; Michael S Lawrence; Gad Getz; Johannes Brägelmann; Rebecca DeBoer; Ralph R Weichselbaum; Alexander Langerman; Louis Portugal; Elizabeth Blair; Kerstin Stenson; Mark W Lingen; Ezra E W Cohen; Everett E Vokes; Kevin P White; Peter S Hammerman Journal: Clin Cancer Res Date: 2014-07-23 Impact factor: 12.531
Authors: Joseph R Garlich; Pradip De; Nandini Dey; Jing Dong Su; Xiaodong Peng; Antoinette Miller; Ravoori Murali; Yiling Lu; Gordon B Mills; Vikas Kundra; H-K Shu; Qiong Peng; Donald L Durden Journal: Cancer Res Date: 2008-01-01 Impact factor: 12.701