Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer

作者: Ju-Won Roh , Jie Huang , Wei Hu , XiaoYun Yang , Nicholas B. Jennings

DOI: 10.1158/1078-0432.CCR-13-2507

关键词:

摘要: Purpose: Platelet-derived growth factor receptor α (PDGFRα) expression is frequently observed in many kinds of cancer and a candidate for therapeutic targeting. This preclinical study evaluated the biologic significance PDGFRα blockade (using fully humanized monoclonal antibody, 3G3) uterine cancer. Experimental Design: Expression was examined clinical samples cell lines, effects inhibition were using vitro (cell viability, apoptosis, invasion) vivo (orthotopic) models Results: highly expressed activated lines. Treatment with 3G3 resulted substantial phosphorylation downstream signaling molecules AKT mitogen-activated protein kinase (MAPK). Cell viability invasive potential cells also inhibited by treatment. In orthotopic mouse cancer, monotherapy had significant antitumor PDGFRα-positive (Hec-1A, Ishikawa, Spec-2) but not PDGFRα-negative model (OVCA432). Greater combination chemotherapy than either drug alone models. The therapy related to increased apoptosis decreased proliferation angiogenesis. Conclusions: These findings identify as an attractive target development Clin Cancer Res; 20(10); 2740–50. ©2014 AACR .

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