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血府逐瘀汤通过调节肿瘤微环境抑制胶质瘤细胞转移和侵袭,发挥抗肿瘤作用。

XuefuZhuyu Tang exerts antitumor effects by inhibiting glioma cell metastasis and invasion via regulating tumor microenvironment.

作者信息

Liu Jianmin, Zhang Ji, Huang Liangwen, Zhu Xuhong, Chen Wei, Hu Peng

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, People's Republic of China.

Department of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

出版信息

Onco Targets Ther. 2016 Jun 17;9:3603-12. doi: 10.2147/OTT.S104108. eCollection 2016.

Abstract

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.

摘要

背景

血府逐瘀汤(XZT)是一种用于活血化瘀的传统中药,目前正用于肿瘤治疗。本研究旨在评估血府逐瘀汤对胶质瘤的影响及其抗癌机制。

材料与方法

将U251细胞分为五组:CNC组(细胞用生理盐水培养)、TSC组(细胞用桃红四物汤[TST]处理)、XSC组(细胞用血府逐瘀汤处理)、THC组(细胞用桃红四物汤匀浆处理)和XHC组(细胞用血府逐瘀汤匀浆处理)。分别通过逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法检测VEGF/VEGFR、CXCR4/CXCL12和TIMP1/MMP9/MMP2的mRNA和蛋白表达。此外,进行MTT法、Transwell法、划痕愈合实验和流式细胞术分别评估U251细胞的细胞活力、细胞迁移和侵袭、细胞运动能力以及细胞凋亡情况。在体内,建立异种移植小鼠模型后构建三种小鼠模型(CNM组,灌胃生理盐水;TSM组,灌胃桃红四物汤;XZM组,灌胃血府逐瘀汤)。然后,采用苏木精-伊红染色、RT-PCR和蛋白质免疫印迹法对模型进行检测。

结果

在体外,血府逐瘀汤显著上调U251细胞中TIMP1的表达,并下调VEGF、VEGFR、CXCR4、CXCL12、MMP9和MMP2的表达(均P<0.05)。此外,血府逐瘀汤抑制细胞增殖、侵袭和迁移,并诱导细胞凋亡。在体内,与对照组和TSM组相比,XZM组中VEGF、CXCL12、MMP9和MMP2的平均表达水平下调(均P<0.05)。XZM组的肿瘤体积显著低于CNM组和TSM组(均P<0.05)。

结论

血府逐瘀汤可能抑制胶质瘤生长,并降低VEGF、CXCL12、MMP9和MMP2的表达水平。我们推测血府逐瘀汤可能是一种治疗胶质瘤的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26bb/4918735/fc60d61f1936/ott-9-3603Fig1.jpg

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