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

초록

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 and Methods: 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 CK2 alpha signals were measured by western blotting. Treatment was carried-out using siRNA to inhibit CK2 alpha. 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 G(2)/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 CK2 alpha 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.

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