title: c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation.
abstract: Hormone-refractory prostate cancer shows substantial resistance to most conventional therapies including radiotherapy, constitutes a key impediment to curing patients with the disease. c-Met overexpression plays a key role in prostate cancer tumorigenesis and disease progression. Here, we demonstrate that c-Met inhibition by SU11274 could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. The underlying mechanisms of the effects of SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death. Our study is the first to show the effectiveness of combining c-Met inhibition with ionizing radiation to cure hormone-refractory prostate cancer.
authors.affiliation: Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Shaoqian
authors.initials: S
authors.lastname: Sun
authors.forename: Xianshu
authors.initials: X
authors.lastname: Gao
authors.forename: Demin
authors.initials: D
authors.lastname: Zhou
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C478479:((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide); D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; D019859:Proto-Oncogene Proteins c-met