AMG 479, a Novel IGF-1-R Antibody, Inhibits Endometrial Cancer Cell Proliferation Through Disruption of the PI3K/Akt and MAPK Pathways

作者：Mendivil Albert; Zhou Chunxiao; Cantrell Leigh A; Gehrig Paola A; Malloy Kim M; Blok Leen J; Burger Curt W; Bae Jump Victoria L^*

来源：Reproductive Sciences, 2011, 18(9): 832-841.

DOI：10.1177/1933719111398501

• endometrial cancer
• insulin growth factor-1
• insulin growth factor-1 receptor
• phosphatidylinositol 3-kinase/Akt pathway
• mitogen-activated protein kinase pathway
• telomerase

Our goal was to evaluate the therapeutic potential of a novel antibody to the insulin growth factor-1 receptor (IGF-1-R; AMG 479) in endometrial cancer cells. The endometrial cancer cell lines, ECC-1/PRAB72 and RL-95-2, were used. Treatment with AMG 479 (0.02-200 nmol/L) resulted in inhibition of cell proliferation at 72 to 120 hours. Insulin growth factor-1 (0.15-7.5 nmol/L) stimulated growth in both cell lines (range of 15%-42%, P = .0025-.0445), which could be blocked by pretreatment with AMG 479 (mean of 29% for ECC-1/PRAB72, P = .006-.007; mean of 36% for RL-95-2, P = .0002-.0045). AMG 479 suppressed IGF-1-R kinase activity in a dose-dependent manner. Cells treated with AMG 479 underwent either G1 (ECC-1/PRAB72) or G2 (RL-95-2) arrest. AMG 479 decreased human telomerase reverse transcriptase (hTERT) mRNA expression in both endometrial cancer cell lines. Treatment with AMG 479 rapidly blocked IGF-1-induced phosphorylation of IFG-1-R, Akt, and p44/42. Thus, manipulation of the IGF-1-R pathway may serve as a promising therapeutic strategy for the treatment of endometrial cancer.

• 出版日期2011-9