Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA.
Anticancer Res. 2010 Jun;30(6):1905-10.
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.
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.
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.
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.
表皮生长因子受体（EGFR）是抗肿瘤治疗的新的分子靶点。本研究检测了抗 EGFR 抗体西妥昔单抗对两种人雄激素非依赖性前列腺癌细胞系 Du145 和 PC-3 的作用。
用台盼蓝法检测细胞增殖。用流式细胞术检测细胞凋亡和细胞周期谱。用 Western 免疫印迹法检测各种信号分子的表达。
西妥昔单抗（100μg/ml）在 Du145 细胞中通过诱导细胞凋亡导致明显的生长抑制，但在 PC-3 细胞中没有。它导致 EGFR 下调，并抑制 Du145 和 PC-3 细胞中的 EGFR Tyr-845 自身磷酸化。然而，在 Du145 细胞中，EGFR 磷酸化 at Tyr-1173 和 MAPK 44/42 磷酸化被抑制，但在 PC-3 细胞中没有。西妥昔单抗不能抑制两种前列腺癌细胞系中的 Akt 磷酸化。
Du145 细胞对西妥昔单抗只有非常温和的反应，而 PC-3 细胞则表现出耐药性。EGFR 下游信号的持续激活可能导致细胞对西妥昔单抗的耐药性。
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