Pooja Dhupkar1, Melissa Dowling, Keith Cengel, Bin Chen. 1. Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA.
Abstract
AIM: Epidermal growth factor receptor (EGFR) is a novel molecular target for anticancer therapy. This study examined the effects of anti-EGFR antibody cetuximab on two human androgen-independent prostate carcinoma cell lines, Du145 and PC-3. MATERIALS AND METHODS: Cell proliferation was monitored with a trypan blue viability assay. Cell apoptosis and cell cycle profile was evaluated by flow cytometry. The expression of various signaling molecules was examined by Western immunoblotting. RESULTS: Cetuximab (100 microg/ml) caused a significant growth inhibition by inducing cell apoptosis in Du145 cells, but not in PC-3 cells. It caused EGFR down-regulation and inhibited EGFR Tyr-845 autophosphorylation in both Du145 and PC-3 cells. However, EGFR phosphorylation at Tyr-1173 and MAPK 44/42 phosphorylation were inhibited in Du145 cells, but not in PC-3 cells. Cetuximab was not able to inhibit Akt phosphorylation in either prostate cancer cell line. CONCLUSION: Du145 cells only showed a very moderate response to cetuximab whereas PC-3 cells showed resistance. Persistent activation of EGFR downstream signaling likely contributes to cell resistance to cetuximab.
AIM: Epidermal growth factor receptor (EGFR) is a novel molecular target for anticancer therapy. This study examined the effects of anti-EGFR antibody cetuximab on two human androgen-independent prostate carcinoma cell lines, Du145 and PC-3. MATERIALS AND METHODS: Cell proliferation was monitored with a trypan blue viability assay. Cell apoptosis and cell cycle profile was evaluated by flow cytometry. The expression of various signaling molecules was examined by Western immunoblotting. RESULTS:Cetuximab (100 microg/ml) caused a significant growth inhibition by inducing cell apoptosis in Du145 cells, but not in PC-3 cells. It caused EGFR down-regulation and inhibited EGFRTyr-845 autophosphorylation in both Du145 and PC-3 cells. However, EGFR phosphorylation at Tyr-1173 and MAPK 44/42 phosphorylation were inhibited in Du145 cells, but not in PC-3 cells. Cetuximab was not able to inhibit Akt phosphorylation in either prostate cancer cell line. CONCLUSION: Du145 cells only showed a very moderate response to cetuximab whereas PC-3 cells showed resistance. Persistent activation of EGFR downstream signaling likely contributes to cell resistance to cetuximab.
Authors: Agnieszka Weinandy; Marc D Piroth; Anand Goswami; Kay Nolte; Bernd Sellhaus; Jose Gerardo-Nava; Michael Eble; Stefan Weinandy; Christian Cornelissen; Hans Clusmann; Bernhard Lüscher; Joachim Weis Journal: Neoplasia Date: 2014-04-13 Impact factor: 5.715
Authors: Steffen Wedel; Lukasz Hudak; Jens-Michael Seibel; Jasmina Makarević; Eva Juengel; Igor Tsaur; Ana Waaga-Gasser; Axel Haferkamp; Roman A Blaheta Journal: BMC Cancer Date: 2011-08-25 Impact factor: 4.430