PP2A inhibitors trigger apoptosis of pancreatic cancer PANC-1 cells through nuclear factor-κB-de- pendent pathway

Abstract

Objective To investigate the action mechanism of protein phosphatase 2A （PP2A） inhibitors inducing apoptosis of pancreatic cancer cell line PANC-1. Methods Cell viability was deter- mined by methyl thiazol tetrazolium （MTT） assay. Activation of nuclear factor-κB （NF-κB） pathway was tested by Western blotting. Apoptosis was tested by flow cytometry. Results Treatment with PP2A inhibitots repressed the cell viability of PANC-1 cells in a dose- and time-dependent manner. PP2A inhibitors also triggered apoptosis in pancreatic cancer cells. Treatment with PP2A inhibitors induced activation of NF-KB pathway through phosphorylation of IKKoL, phosphorylation and degradation of IKBα, and nuclear translocation of p65. The cytotoxicity of PP2A inhibitors could be attenuated by the inhibitor of NF-KB pathway. Conclusion PP2A inhibitors triggered apoptosis of pancreatic cancer cells through NF-κB-de- pendent pathway, making PP2A an attractive target for pancreatic cancer therapy. Key words: PP2A inhibitor;  Pancreatic carcinoma;  NF-κB