Additive antiangiogenesis effect of ginsenoside Rg3 with low-dose metronomic temozolomide on rat glioma cells both in vivo and in vitroReportar como inadecuado

Additive antiangiogenesis effect of ginsenoside Rg3 with low-dose metronomic temozolomide on rat glioma cells both in vivo and in vitro - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Experimental and Clinical Cancer Research

, 35:32

First Online: 13 February 2016Received: 29 October 2015Accepted: 17 December 2015DOI: 10.1186-s13046-015-0274-y

Cite this article as: Sun, C., Yu, Y., Wang, L. et al. J Exp Clin Cancer Res 2016 35: 32. doi:10.1186-s13046-015-0274-y


BackgroundGlioblastoma is the most common and deadly primary brain tumor in adults. Low-dose,metronomic LDM temozolomide TMZ displays improved efficacy in the treatment of glioblastoma by targeting angiogenesis, but has a limited effect on recurrence. The antiangiogenesis drug ginsenoside Rg3 RG3 is the main active ingredient of ginseng, a popular herbal medicine.

MethodsUsing an in vitro and a rat model of an orthotopic glioma allograft, this study was to determine whether RG3 enhanced the antiangiogenesis activity of LDM TMZ in the treatment of glioblastoma.

ResultsOur results showed that combined use of TMZ with RG3 displayed additive inhibition on proliferation of both human umbilical vein endothelial cells HUVEC and rat C6 glioma cells in vitro. They additively arrested cell cycle, increased apoptosis, and decreased VEGF-A and BCL-2 expression in HUVEC. Antiangiogenesis effect was also evaluated in the rat model of orthotopic glioma allograft, based upon markers including relative cerebral blood volume rCBV by magnetic resonance imaging MRI, VEGF levels and microvessel density MVD-CD34 staining. LDM TMZ alone was potent in suppressing angiogenesis and tumor growth, whereas RG3 alone only had modest antiangiogenesis effects. Combined treatment significantly and additively suppressed angiogenesis, without additive inhibitory effects on allografted tumor growth.

ConclusionsThese data provide evidence showing the efficacy of LDM TMZ on glioma treatment. The combined additive antiangiogenesis effect suggests that RG3 has the potential to further increase the efficacy of LDM TMZ in the treatment of glioblastoma.

KeywordsTMZ RG3 Glioblastoma Metronomic Angiogenesis VEGF Allograft rCBV AbbreviationsFCMFlow cytometry

HUVECHuman umbilical vein endothelial cells

LDMLow dose metronomic

MRIMagnetic resonance imaging

MTDMaximum tolerated dose

ODOptical density

rCBVRelative cerebral blood volume


Electronic supplementary materialThe online version of this article doi:10.1186-s13046-015-0274-y contains supplementary material, which is available to authorized users.

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Autor: Caixing Sun - Yang Yu - Lizhen Wang - Bin Wu - Liang Xia - Fang Feng - Zhiqiang Ling - Shihua Wang


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