Activation of NFB occurs

Activation of NFB occurs http://www.selleckchem.com/products/Nilotinib.html via phosphorylation of IB at Ser32 and Ser36. This is followed by prote asome mediated degradation resulting in release and nuclear translocation of active NFB, where it regulates expression of several pro survival or pro apoptotic pro teins, e. g, pIkB, pbcl 2, bcl xL, xIAP. Expression of pNFkB, pIkB, XIAP, pbcl 2 and bcl xL were assessed by western blotting. pNFkB was detected using a specific antibody that detects NFB p65 only when Inhibitors,Modulators,Libraries phosphory lated at Ser536. Similarly, expression of phosphoIkB was detected using a monoclonal antibody that detects endogenous levels of IB only when phosphorylated at Ser32. As described in Figure 7A, pro survival marker, phospho NFB p65, showed decreased expression at 24 hrs post BT treatment in all cell lines at 100 uM BT.

Similarly, pIB levels were reduced at 24 hrs Inhibitors,Modulators,Libraries post treatment. The extent of decrease varied between cell lines with a significant decrease observed in A2780, SKOV 3 and OVACAR 3. Compared to all cell lines, A2780 CDDP showed weak expression of pIkB at all concentrations. Interestingly, down regulation of several genes regulated by NFB was observed in all cell lines. BT at 100 uM consistently inhibited pbcl 2 and bcl xL in all cell lines. Phospho Bcl 2 was detected using an antibody that de tects Bcl 2 only when phosphorylated at threonine56. Expression of pro survival marker XIAP, a direct inhibi tor of executioner Inhibitors,Modulators,Libraries caspases, such as caspase 3, was down regulated within 24 hrs following the BT treat ment in all the cell lines. Effect of BT on autotaxin inhibition BT treatment significantly inhibited ATX in all the cell lines tested.

BT induced ATX inhibition was time dependent as more inhibition was observed at 48 hrs post treatment than at 24 hrs. Approximately 40 60% inhibition was observed Inhibitors,Modulators,Libraries at 100 uM BT at 48 hrs post treatment in all cell lines tested. The ex tent of ATX inhibition was nearly similar in all cell lines. Discussion Drug resistance is a major cause for ovarian cancer re currence. New drug discovery requires significant re sources and time. Alternatively, the concept of drug repurposing appears promising. In the present study, we explored the antitumor potential of BT in pre clinical ovarian cancer model. BT was tested against a panel of ovarian cancer lines exhibiting varying sensitivities to cisplatin.

Our results demonstrate the cytotoxic effects of BT towards all the ovarian cancer cells lines tested with IC50 values ranging from 19 uM to 60 uM, at 72 hrs post treatment. Interestingly, BT IC50 values Inhibitors,Modulators,Libraries were almost indistinguishable between cisplatin http://www.selleckchem.com/products/Abiraterone.html sensitive and cisplatin resistant variants of isogenic ovarian cancer cell line pairs, although cisplatin IC50 values varied signifi cantly. These results are significant when considering that clinically, all recurrent ovarian cancers will eventu ally be platinum resistant.

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