Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1.

ABSTRACT:

Aims

To evaluate the antitumor and antiangiogenic activity of metronomic ceramide analogs and their relevant molecular mechanisms.

Methods

Human endothelial cells [human dermal microvascular endothelial cells and human umbilical vascular endothelial cell (HUVEC)] and pancreatic cancer cells (Capan-1 and MIA PaCa-2) were treated with the ceramide analogs (C2, AL6, C6, and C8), at low concentrations for 144 hours to evaluate any antiproliferative and proapoptotic effects and inhibition of migration and to measure the expression of caveolin-1 (CAV-1) and thrombospondin-1 (TSP-1) mRNAs by real-time reverse transcription-polymerase chain reaction. Assessment of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Akt phosphorylation and of CAV-1 and cyclin D1 protein expre

SUBMITTER: Bocci G 

PROVIDER: S-EPMC3459279 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature