This data is for laboratory research purposes only. Not for human or animal consumption.
What is DES(1-3) IGF-1?
DES(1-3) IGF-1 (also called Des(1-3)-IGF-1 or Long R3-IGF-1) is a synthetic analog of insulin-like growth factor-1 (IGF-1) that selectively activates the IGF-1 receptor (IGF1R) with reduced binding to insulin-like growth factor binding proteins (IGFBPs). In this research context, it was used as a pharmacological tool to study IGF1R-mediated resistance mechanisms in oral squamous cell carcinoma (OSCC) cells treated with EGFR tyrosine kinase inhibitors.
Mechanism of Action
DES(1-3) IGF-1 binds directly to IGF1R, triggering downstream activation of PI3K/AKT and MAPK/ERK signaling pathways. In OSCC cells, IGF1R activation antagonizes EGFR-TKI-induced cell cycle arrest by phosphorylating p27 (CDK inhibitor 1B) at the T157 residue, promoting cytoplasmic translocation of p27 and reducing its nuclear accumulation. This relocalization converts p27 from a cell cycle inhibitor to a promoter of cell proliferation and motility, effectively rescuing cancer cells from gefitinib-mediated growth suppression.
Observed Laboratory Results
- S-phase population reversal: IGF1R activation via DES(1-3) IGF-1 induced a 2.8-fold increase in S-phase cells, reversing the 50% S-phase reduction caused by gefitinib monotherapy in SCC-25 OSCC cells.
- p27 phosphorylation state alteration: Gefitinib decreased pT157-p27 levels, but concurrent IGF1R stimulation reversed this phosphorylation, enabling cytoplasmic sequestration of p27 despite elevated total p27 protein.
- Subcellular p27 redistribution: Both subcellular fractionation and immunofluorescence microscopy demonstrated that DES(1-3) IGF-1 significantly increased cytoplasmic localization of p27, which persisted during combined gefitinib + IGF1R stimulation treatment.