OncoTargets and Therapy (Jun 2016)
XuefuZhuyu Tang exerts antitumor effects by inhibiting glioma cell metastasis and invasion via regulating tumor microenvironment
Abstract
Jianmin Liu,1 Ji Zhang,2 Liangwen Huang,1 Xuhong Zhu,1 Wei Chen,1 Peng Hu1 1Department of Neurosurgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 2Department of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China Background: XuefuZhuyu Tang (XZT) is a traditional Chinese herb used for destagnation and is currently being used for oncotherapy. This study was intended to assess the effects of XZT on glioma along with its anticancer mechanism.Materials and methods: U251 cells were divided into five groups: CNC (cells were cultured with normal saline), TSC (cells were treated with TaohongSiwu Tang [TST]), XSC (cells were treated with XZT), THC (cells were treated with homogenate of TST), and XHC (cells were treated with homogenate of XZT). The mRNA and protein expression of VEGF/VEGFR, CXCR4/CXCL12, and TIMP1/MMP9/MMP2 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, MTT assay, transwell assay, wound-healing assay, and flow cytometry were conducted to assess the cell viability, cell migration and invasion, cell motility, and cell apoptosis of U251 cells, respectively. In vivo, three mice models (group CNM, gavaging saline; group TSM, gavaging TST; group XZM, gavaging XZT) were constructed after establishing xenograft mice models. Then, models were examined using hematoxylin and eosin staining, RT-PCR, and Western blotting. Results: In vitro, XZT significantly upregulated TIMP1 expression and downregulated the expression of VEGF, VEGFR, CXCR4, CXCL12, MMP9, and MMP2 in U251 cells (all P<0.05). In addition, XZT inhibited cell proliferation, invasion, and migration and induced cell apoptosis. In vivo, the average expression level of VEGF, CXCL12, MMP9, and MMP2 was downregulated in the XZM group compared with the control and TSM groups (all P<0.05). Tumor volumes in the XZM group were significantly lower than those in the CNM and TSM groups (all P<0.05). Conclusion: XZT may suppress glioma growth and decrease expression levels of VEGF, CXCL12, MMP9, and MMP2. We speculate that XZT may be a potential therapeutic herb for curing glioma. Keywords: XuefuZhuyu Tang, glioma, tumor microenvironment, VEGF, CXCL12, TIMP1, MMP9, MMP2
