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Ref Type Journal Article
PMID (30316146)
Authors Zakharia K, Miyabe K, Wang Y, Wu D, Moser CD, Borad MJ, Roberts LR
Title Preclinical In Vitro and In Vivo Evidence of an Antitumor Effect of CX-4945, a Casein Kinase II Inhibitor, in Cholangiocarcinoma.
Journal Vol Issue Date Pages Journal Short Title
Translational oncology 12 1 2018 Oct 10 143-153 Transl Oncol
URL
Abstract Text We investigated the antitumor effect of the casein kinase II (CK2) inhibitor CX-4945 on cholangiocarcinoma (CCA).We assessed the effect of CX-4945 alone and/or in combination with gemcitabine and cisplatin on cell viability, colony formation, and apoptosis of CCA cell lines and on in vivo growth of HuCCT1 xenografts.CX-4945 dose-dependently decreased viability of HuCCT1, EGI-1, and Liv27 and decreased phospho-AKT/total AKT and phospho-PTEN/total PTEN ratios. CX-4945 significantly increased caspase 3/7 activity in a dose- and time-dependent manner. CX-4945 significantly enhanced the effect of gemcitabine or cisplatin on HuCCT1, EGI-1, and Liv27 cells and inhibited the phosphorylation of DNA repairing enzymes XRCC1 and MDC1. Further, CX-4945 alone significantly inhibited growth of HuCCT1 mouse xenograft tumors. Combining CX-4945 with gemcitabine and cisplatin was more potent than CX-4945 alone or gemcitabine/cisplatin. The effect of CX-4945 on cell proliferation, apoptosis, the PI3K/AKT pathway, and DNA repair was confirmed in the mouse xenografts.CX-4945 has an antiproliferative effect on CCA and enhances the effect of gemcitabine and cisplatin through its inhibitory effect on the PI3K/AKT pathway and DNA repair.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References