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AKT/mTOR Down-regulation by CX-4945, a CK2 Inhibitor, Promotes Apoptosis in Chemorefractory Non-small Cell Lung Cancer Cells.

By: Kwang Sup So, Jin Kyung Rho, Yun Jung Choi, Seon Ye Kim, Chang Min Choi, Young Jin Chun, Jae Cheol Lee

Department of Pulmonary and Critical Care Medicine, University of Ulsan, Seoul, Republic of Korea College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
2015-3-10; doi:

Abstract

Aim

The response to chemotherapeutic drugs in non-small cell lung cancer (NSCLC) is unsatisfactory, leading to poor outcomes. This study the aimed to investigates anticancer effects of CX-4945, a potent casein kinase II (CK2) inhibitor, in chemorefractory NSCLC cells.

Materials

Cell proliferation and apoptosis assay were carried-out by annexin V-FITC and FACScan after drug treatment with paclitaxel, cisplatin and CX-4945. AKT/mTOR and CK2α signals were measured by western blotting. Treatment was carried-out using siRNA to inhibit CK2α.

Results

Paclitaxel, and cisplatin effectively inhibited cell proliferation and induced apoptosis in A549 cells, while not in H1299, Calu-1 and H358 cells. In these chemorefractory cell lines, AKT signalling was maintained despite drug treatment. However, CX-4945 suppressed cell growth, with cell-cycle arrest at G2/M phase and induced apoptosis with an increase of cleaved caspase-3 and PARP1 in a dose-dependent manner. Accordingly, AKT and its downstream signals such as mTOR and p70S6K were down-regulated by CX-4945. Transfection of CK2α siRNA had similar effects to CX-4945 treatment on cell proliferation and apoptosis.

Conclusion

CX-4945 shows a promising anticancer action through down-regulation of AKT/mTOR signals, suggesting its possible application for treatment of chemorefractory lung cancer.