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Autophagy Induced by CX-4945, a Casein Kinase 2 Inhibitor, Enhances Apoptosis in Pancreatic Cancer Cell Lines

Objectives Pancreatic cancer is the most lethal malignancy with only a few effective chemotherapeutic drugs. Because the inhibition of casein kinase 2 (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, 8902, MIA PaCa-2 human pancreatic cancer cell lines, and CX-4945, a novel CK2 inhibitor, were used. 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 cells. This suppression of proliferation was caused by the direct inhibition of CK2&agr;, which was required for autophagy and apoptosis in 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 3-methyladenine or small interfering RNA against Atg7, which attenuated apoptosis in pancreatic cancer cells. Conclusions 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.