Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway

<p>Abstract</p> <p>Background</p> <p>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) o...

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Main Authors: Du Wei, Zhou Jing-ru, Wang Dong-liang, Gong Kai, Zhang Qing-jun
Format: Article
Language:English
Published: BMC 2012-04-01
Series:World Journal of Surgical Oncology
Subjects:
Online Access:http://www.wjso.com/content/10/1/60
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author Du Wei
Zhou Jing-ru
Wang Dong-liang
Gong Kai
Zhang Qing-jun
author_facet Du Wei
Zhou Jing-ru
Wang Dong-liang
Gong Kai
Zhang Qing-jun
author_sort Du Wei
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We 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.</p> <p>Results</p> <p>Sorafenib, 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.</p> <p>Conclusions</p> <p>Our 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.</p>
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spelling doaj.art-cb0011b499b94ad5afa17616e3195faf2022-12-22T01:17:37ZengBMCWorld Journal of Surgical Oncology1477-78192012-04-011016010.1186/1477-7819-10-60Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathwayDu WeiZhou Jing-ruWang Dong-liangGong KaiZhang Qing-jun<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We 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.</p> <p>Results</p> <p>Sorafenib, 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.</p> <p>Conclusions</p> <p>Our 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.</p>http://www.wjso.com/content/10/1/60ApoptosisGliomaMAPKSorafenibVitamin K1
spellingShingle Du Wei
Zhou Jing-ru
Wang Dong-liang
Gong Kai
Zhang Qing-jun
Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway
World Journal of Surgical Oncology
Apoptosis
Glioma
MAPK
Sorafenib
Vitamin K1
title Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway
title_full Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway
title_fullStr Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway
title_full_unstemmed Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway
title_short Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway
title_sort vitamin k1 enhances sorafenib induced growth inhibition and apoptosis of human malignant glioma cells by blocking the raf mek erk pathway
topic Apoptosis
Glioma
MAPK
Sorafenib
Vitamin K1
url http://www.wjso.com/content/10/1/60
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AT wangdongliang vitamink1enhancessorafenibinducedgrowthinhibitionandapoptosisofhumanmalignantgliomacellsbyblockingtherafmekerkpathway
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