In vitro and in vivo radiosensitization of colorectal cancer HT-29 cells by the smac mimetic JP-1201

Surgery
Sergio HuertaThomas Anthony

Abstract

The response to neoadjuvant chemoradiation in rectal cancer is variable and unpredictable. Resistance to chemoradiation has been directly correlated with the levels of the inhibitors of apoptosis (IAPs) in several malignancies. Because smac-DIABLO is a pro-apoptotic gene product that directly inhibits the activity of the IAPs, molecules with similar activity might radiosensitize rectal tumors with phenotypes that express high levels of IAPs. This study was undertaken to assess the radiosensitizing properties of the smac mimetic JP-1201 in radioresistant HT-29 colorectal cancer cells in vitro and established xenografts in SCID mice. Survival was determined by clonogenic assays. PARP-1, caspase-8 cleavage, and IAP levels were assessed by Western blot analysis. SCID mice bearing HT-29 xenografts were treated with ionizing radiation: 2.0 Gy x 5; (n = 6), JP-1201 (5.0 mg/Kg i.p., n = 5) or combination treatment (n = 7) and compared to control (n = 8). DNA repair mechanisms were interrogated by gammaH2AX positive foci. Pretreatment of HT-29 cells with JP-1201 (5.0 microM) prior to ionizing radiation (IR) significantly decreased the survival of these cells. SCID mice bearing HT-29 xenografts demonstrated no difference in tumor load in...Continue Reading

References

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Citations

Oct 31, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qin QinXinchen Sun
Oct 20, 2010·The Journal of Biological Chemistry·Herman H CheungRobert G Korneluk
Jul 16, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Wenyan LiBo Lu
Apr 1, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Samira GoldarBehzad Baradaran
Mar 13, 2014·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Stamatia Pouliliou, Michael I Koukourakis
May 1, 2015·Radiation Oncology·Simone Fulda
Mar 28, 2012·Pharmaceutical Research·Michael DanquahRam I Mahato
May 1, 2011·Oncology Letters·Kazuhito SasakiHirokazu Nagawa
Apr 10, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Hadi Esmaeili Govarchin GhalehNasrollah Jabbari

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