CX-4945, a CK2 inhibitor, Enhances Autophagy and Apoptosis in Pancreatic Cancer Cell Lines

Abstract

Background: Pancreatic cancer is the most lethal malignancy, with an overall 5-year survival rate of less than 5%. Although the need for more effective systemic therapeutics has long existed, there is only a marginal survival benefit from available adjuvant therapies. Because the inhibition of protein kinase CK2 has been reported as a novel therapeutic strategy for many cancers, we investigated the effects of CK2 inhibitors in pancreatic cancer cell lines. Methods: The BxPC3, PATU8902 and Miapaca2 human pancreatic cancer cell lines were used in our experiments. CX-4945 was used as a novel CK2 inhibitor. Autophagy was analyzed by acridine orange staining, fluorescence microscope detection of punctuate patterns of GFP-tagged LC3 and immunoblotting for LC3. Cell survival, cell cycle and apoptosis analysis was performed. Results: CX-4945 induced significant inhibition of proliferation and triggered autophagy in pancreatic cancer cell lines. This inhibition of proliferation was caused by direct inhibition of CK2α, which was required for autophagy and apoptosis in the pancreatic cancer cells. CX-4945 suppressed cell cycle progression in G2/M and induced apoptosis. The inhibition of CX-4945-induced autophagy was rescued by 3MA or siRNA against Atg7, which attenuated apoptosis in the pancreatic cancer cells. Conclusion: CX-4945, a potent and selective inhibitor of CK2, effectively induces autophagy and apoptosis in pancreatic cancer cells, indicating that the induction of autophagy by CX-4945 may have an important role in the treatment of pancreatic cancer.