For selleck chem Dasatinib this assay, cells were grown in selleck screening library medium containing 2% FBS selleck chemical as in growth inhibition stud ies with other agents. We have shown previously that, at nM concentrations, Inhibitors,Modulators,Libraries EGFR ligands inhibit the growth of EGFR overexpressing tumour cell lines in vitro. To con firm the bioactivity of exogenous HER ligands, we examined their effects on the growth of EGFR overexpressing Inhibitors,Modulators,Libraries HN5 cells. All HER ligands, except NRG 1, inhibited the growth of HN5 cells in vitro. In addition, with the excep tion of BxPC3 and AsPc 1 cell lines which exhibited signifi cant growth response to NRG 1, the majority of pancreatic tumour cell lines did not respond to treatment with the ex ogenous HER ligands or exhibited very low increase in cell proliferation.

Interestingly Inhibitors,Modulators,Libraries AsPc 1 was the only cell line which exhibited increased growth after treatment with epigen.

Inhibitors,Modulators,Libraries Of all cell lines examined here, only BxPc3,AsPc1, Capan 1 Inhibitors,Modulators,Libraries and Inhibitors,Modulators,Libraries PT45 cell lines demon strated significant increase in growth after treat ment with IGF I, IGF II or insulin. Growth response Inhibitors,Modulators,Libraries of human pancreatic tumour cells to treatment with NVP AEW541 as a single agent or in combination Inhibitors,Modulators,Libraries with gemcitabine, afatinib and ICR62 We have reported recently the effect of afatinib, erlotinib, ICR62 and gemcitabine on the growth of pancreatic cancer cell lines. Of these agents gemcitabine exhibited the highest anti proliferative activity with IC50 values at the low nanomolar range while afatinib with a Inhibitors,Modulators,Libraries range of IC50 values from 11nM to 1.

37 uM demonstra ted a higher Inhibitors,Modulators,Libraries anti tumour activity compared Inhibitors,Modulators,Libraries to first gene ration EGFR TKI erlotinib.

Inhibitors,Modulators,Libraries Here we investigated the growth response of the same panel of pancreatic cancer cell lines to treatment with NVP AEW541 an IGF IR TKI. Of 7 human pancreatic tumour cell lines examined, FA6 cells were the Inhibitors,Modulators,Libraries most sensitive Inhibitors,Modulators,Libraries cell line to treatment with NVP Inhibitors,Modulators,Libraries AEW541 with an IC50 value of 342 nM. The IC50 values for the rest of the cell lines ranged from 897 nM to 2. 73 uM. Median effect analysis selleckchem Gefitinib showed that a combination of NVP AEW541 with gemcitabine led to a synergistic or additive growth inhibition of 4 out of 7 human pancre atic tumour cell lines.

We found no enhance ment of growth inhibition following treatment with a combination of ICR62 with NVP AEW541. Interestingly, with the exception of PT 45, the combination of the IGF IR inhibitor NVP AEW541 with afatinib selleck products was superior to that of NVP AEW541 with gemcitabine leading to synergistic growth inhibition of together all pancreatic cancer cell lines. How ever, this was statistically significant in four cell lines.