Abstract

BackgroundThe combined effects of anticancer drugs with nutritional factors against tumor cells have been reported previously. This study characterized the efficacy and possible mechanisms of the combination of sorafenib and vitamin K1 (VK1) on glioma cell lines.MethodsWe examined the effects of sorafenib, VK1 or their combination on the proliferation and apoptosis of human malignant glioma cell lines (BT325 and U251) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) assay. The signaling pathway changes were detected by western blotting.ResultsSorafenib, as a single agent, showed antitumor activity in a dose-dependent manner in glioma cells, but the effects were more pronounced when used in combination with VK1 treatment. Sorafenib in combination with VK1 treatment produced marked potentiation of growth inhibition and apoptosis, and reduced expression of phospho-mitogen-activated protein kinase kinase (MEK) and phospho-extracellular signal-regulated kinase (ERK). Furthermore, the expression levels of antiapoptotic proteins Bcl-2 and Mcl-1 were significantly reduced.ConclusionsOur findings indicated that VK1 enhanced the cytotoxicity effect of sorafenib through inhibiting the Raf/MEK/ERK signaling pathway in glioma cells, and suggested that sorafenib in combination with VK1 maybe a new therapeutic option for patients with gliomas.

Highlights

  • The combined effects of anticancer drugs with nutritional factors against tumor cells have been reported previously

  • Inhibition of glioma cell growth by sorafenib plus vitamin K1 (VK1) In order to investigate the impact of sorafenib plus VK1 on the proliferation of glioma cells, we exposed BT325 and U251 cells to the studied agents, either individually or in combination

  • MTT assays indicated that VK1 is Induction of glioma cell apoptosis by sorafenib plus VK1 Apoptosis is the major consequence of tumor cells exposed to chemotherapy agents

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Summary

Introduction

The combined effects of anticancer drugs with nutritional factors against tumor cells have been reported previously. This study characterized the efficacy and possible mechanisms of the combination of sorafenib and vitamin K1 (VK1) on glioma cell lines. Malignant gliomas are the most prevalent primary brain tumors in adults, exhibiting a high rate of cell proliferation and migration activities [1]. Whereas sorafenib treatment of glioma cell lines and tumor xenografts results in cell growth inhibition and tumor growth regression [12,13], its use in the clinical treatment of patients with malignant gliomas has yielded disappointing results [14]. Despite its relative ineffectiveness in patients with malignant gliomas, the ability of sorafenib to inhibit tumor cell proliferation suggests that it may be useful in combination with other therapeutic agents

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