Effects of anti-EGFR antibody cetuximab on androgen-independent prostate cancer cells.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Dhupkar
Pooja
P
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA.
Dowling
Melissa
M
Cengel
Keith
K
Chen
Bin
B
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000068818:Cetuximab