title: Effect of combining anti-epidermal growth factor receptor antibody C225 and radiation on DU145 prostate cancer.
abstract: The epidermal growth factor receptor (EGFR) network has rich targets for prostate cancer killing. Herein we evaluated the effects of combining the EGFR inhibition and radiation on DU145 prostate cancer. We treated DU145 prostate cancer cells with various doses of anti-EGFR antibody (C225) and gamma-irradiation (RAD). The effects of the treatment on cell viability and growth were assessed with cell counting, XTT and clonogenic assays. In vivo treatment effects were assessed using a subcutaneous tumor xenograft in mice. Cell cycle distribution and progression were assessed with flow cytometry. The apoptotic components of cell death were quantified using Annexin-V binding assays. The results demonstrated that when combined with radiation, C225 augmented the inhibition of cell viability and growth in the DU145 cell line and EGFR inhibition appeared to have some interaction with RAD. C225 inhibited the growth of implanted DU145 tumors and increased the efficacy of radiation treatment. Flow cytometric analysis suggested that mostly necrotic cell death resulted from the EGFR inhibition or irradiation, although there may be some apoptosis. We drew the conclusion that the inhibition of EGFR augments the radiation killing of DU145 prostate cancer via a combination of cytostatic, necrotic and apoptotic mechanisms.
authors.affiliation: Department of Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wagener
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Humberto G
authors.initials: HG
authors.lastname: Villarreal
authors.forename: Larry
authors.initials: L
authors.lastname: Levy
authors.forename: Pamela
authors.initials: P
authors.lastname: Allen
authors.forename: Shujun
authors.initials: S
authors.lastname: Shentu
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
authors.forename: M Rex
authors.initials: MR
authors.lastname: Cheung
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000532:radiotherapy* / Q000628:therapy*
chemical_list: D017304:Annexin A5; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D000068818:Cetuximab