title: Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells.
abstract: Colorectal cancer is one of the most common cancers worldwide. Previous studies suggest that chemoradiotherapy is more effective for the treatment of colorectal cancer than is radiotherapy or chemotherapy alone. To enhance the radiosensitivity of tumor cells, several investigators have used targeted therapeutic agents that act as radiosensitizers. In the present study, we provide a scientific rationale for the clinical application of SU5416, an inhibitor of vascular endothelial growth factor receptor-2, as a radiosensitizer for colorectal cancer. Two human colorectal adenocarcinoma cell lines, HCT116 and HT-29, were treated with SU5416 and radiation alone or radiation followed by SU5416. In vitro tests were performed using colony forming assays, flow cytometric analysis, immunohistochemistry, senescence-associated β-galactosidase, tumor cell motility and invasion assays. The combination of radiation and SU5416 synergistically inhibited cell survival and induced apoptosis through reactive oxygen species, enhanced IR-induced premature senescence, and inhibited DNA repair activity, cell migration and invasion. Collectively, our results favor the use of SU5416 and radiotherapy as a combination therapy for the treatment of colon cancer and it can be combined successfully with a radiation regimen to potentiate its antitumor and antimetastatic activities for future clinical trials.
authors.affiliation: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Nowon-Ku, Seoul 139-706, Republic of Korea.
authors.forename: Eun Ho
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Nowon-Ku, Seoul 139-706, Republic of Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Lee
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Nowon-Ku, Seoul 139-706, Republic of Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Jeong
authors.affiliation: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Nowon-Ku, Seoul 139-706, Republic of Korea.
authors.forename: Won-Gyun
authors.initials: WG
authors.lastname: Jung
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000375:Aging / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C116890:Semaxinib; D040262:Receptors, Vascular Endothelial Growth Factor; D001616:beta-Galactosidase