Inhibition of IGF1R enhances 2-deoxyglucose in the treatment of non-small cell lung cancer.

ABSTRACT:

Objective

We previously postulated that 2-deoxyglucose (2-DG) activates multiple pro-survival pathways through IGF1R to negate its inhibitory effect on glycolysis. Here, we evaluated whether IGF1R inhibitor synergizes with 2-DG to impede the growth of non-small cell lung cancer (NSCLC).

Materials and methods

The activation of IGF1R signaling was assessed by the phosphorylation of IGF1R and its downstream target AKT using immunoblot. Drug dose response and combination index analyses were carried out according to the method of Chou and Talalay. Flow cytometry was used to evaluate cell cycle progression. Apoptosis was monitored by caspase-3/PARP cleavages or Annexin V staining. A subcutaneous xenograft model was used to assess this combination in vivo.

Results

2-DG induc

SUBMITTER: Liu F 

PROVIDER: S-EPMC6447049 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature