Abstract
The present study investigated the effect of AC480, a small molecule pan-HER tyrosine kinase inhibitor, on in vitro radiosensitivity and in vivo radioresponse of a human head and neck squamous cell carcinoma cell line. HN-5 cells were exposed to γ-radiation with and without AC480 and assayed for proliferation, clonogenic survival, apoptosis, cell cycle distribution, and DNA damage. The cells were analyzed by immunoprecipitation and western blotting for proteins involved in apoptosis, cell cycle regulation, and the EGFR pathway. The effect of AC480 on tumor radioresponse was assessed by tumor growth delay assay using HN5 tumor xenografts generated in nude mice. At the molecular level, in HN-5 cells the agent inhibited the expression of pEGFR, pHER2, cyclins D and E, pRb, pAkt, pMAPK, pCDK1 and 2, CDK 6, and Ku70 proteins. The drug also induced accumulation of cells in the G1 cell cycle phase, inhibited cell growth, enhanced radiosensitivity, and prolonged the presence of γ-H₂AX foci up to 24 h after radiation. AC480 did not increase the percentage of cells undergoing radiation-induced apoptosis. The drug given before and during irradiation improved the radioresponse of HN5 tumors in vivo. AC480 significantly enhanced the radiose...Continue Reading
References
Nov 1, 1995·Archives of Otolaryngology--head & Neck Surgery·R N BeckhardtG L Clayman
Sep 19, 1997·Oncogene·R K Schmidt-UllrichP B Chen
Jan 1, 1997·Radiation Oncology Investigations·M T SheridanC E Mothersill
Dec 16, 1998·International Journal of Radiation Biology·U RajuP J Tofilon
Apr 13, 2000·International Journal of Radiation Oncology, Biology, Physics·T AkimotoL Milas
Mar 2, 2002·International Journal of Radiation Oncology, Biology, Physics·Luka MilasK Kian Ang
Nov 15, 2002·The New England Journal of Medicine·Khandan KeyomarsiSarah S Bacus
Aug 12, 2003·International Journal of Radiation Oncology, Biology, Physics·Ke LiangZhen Fan
Feb 18, 2004·International Journal of Radiation Oncology, Biology, Physics·Luka MilasK Kian Ang
May 6, 2004·Cancer Research·Said AkliKhandan Keyomarsi
Aug 4, 2004·Cancer Research·Shyhmin HuangPaul M Harari
Apr 6, 2005·International Journal of Oncology·T EkbergM Anniko
Jul 8, 2005·The Journal of Biological Chemistry·Klaus DittmannH Peter Rodemann
Jul 19, 2005·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Klaus DittmannHans-Peter Rodemann
Jan 7, 2006·Cancer Biology & Therapy·Irina CorinCristiano Simone
Feb 10, 2006·The New England Journal of Medicine·James A BonnerK Kian Ang
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tai W WongGregory D Vite
Dec 13, 2006·Experimental Cell Research·Francesca WalkerAntony W Burgess
Jan 24, 2007·International Journal of Radiation Oncology, Biology, Physics·Luka MilasK Kian Ang
Feb 23, 2007·Head & Neck·Andrea CavalotGiorgio Cortesina
Jul 25, 2007·Cancer·Ben DavidsonVivi Ann Flørenes
Aug 3, 2007·Cancer Research·Said AkliKhandan Keyomarsi
Nov 13, 2007·International Journal of Radiation Oncology, Biology, Physics·Klaus H DittmannH Peter Rodemann
Feb 29, 2008·Journal of Clinical Pathology·A N A MilneG J A Offerhaus
Citations
Sep 14, 2011·PloS One·Somaira NowsheenEddy S Yang
Oct 5, 2011·Expert Opinion on Pharmacotherapy·Antarpreet Kaur, Constantin A Dasanu
Sep 25, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Richard L SchroederJayalakshmi Sridhar
Sep 23, 2014·International Journal of Radiation Biology·Yue JinYong Liang
Nov 29, 2011·Cancer Letters·Somaira NowsheenAlexandros G Georgakilas
Mar 13, 2014·Drug Discovery Today·Saurabh PrabhuTimothy J Snape
Feb 13, 2015·Frontiers in Oncology·Xiaochun WangJia-Lin Yang
Dec 2, 2017·Oncotarget·Rui LiuMeiju Ji