AMG 479, a novel IGF-1-R antibody, inhibits endometrial cancer cell proliferation through disruption of the PI3K/Akt and MAPK pathways
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.
|Keywords||endometrial cancer, insulin growth factor-1, insulin growth factor-1 receptor, mitogen-activated protein kinase pathway, phosphatidylinositol 3-kinase/Akt pathway, telomerase|
|Persistent URL||dx.doi.org/10.1177/1933719111398501, hdl.handle.net/1765/31049|
Mendivil, A, Zhou, C, Cantrell, L.A, Gehrig, P.A, Malloy, K.M, Blok, L.J, … Bae-Jump, V.L. (2011). AMG 479, a novel IGF-1-R antibody, inhibits endometrial cancer cell proliferation through disruption of the PI3K/Akt and MAPK pathways. Reproductive Sciences, 18(9), 832–841. doi:10.1177/1933719111398501