Herbal compound “Songyou Yin” attenuates hepatoma cell invasiveness and metastasis through downregulation of cytokines secreted by activated hepatic stellate cells

BMC Complementary and Alternative Medicine

Zhao-You Tang²  Li-Fen Deng²  Tong-Chun Xue²  Qiang-Bo Zhang²  Lan Zhang²  Yan-Hong Wang²  Xiao-Ying Xie²  Yang Bu¹  Zheng-Gang Ren²  Zhi-Ming Wang²  Qing-An Jia² 

[1] Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China;Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China

关键词: Metastasis;    Hepatic stellate cells;    Herbal compound;    Hepatocellular carcinoma;   

Others  :  1230067
DOI  :  10.1186/1472-6882-13-89

 received in 2012-10-05, accepted in 2013-04-17,  发布年份 2013

【 摘 要 】

Background

Activated hepatic stellate cells (aHSCs) play an important role in the progression of hepatocellular carcinoma (HCC). Here, we determined if cytokines secreted in response to the herbal compound “Songyou Yin” (SYY) treatment of aHSCs could influence invasiveness and metastatic capabilities of hepatoma cells.

Methods

Primary rat hepatic stellate cells (HSCs) were isolated, activated, divided into SYY treated and untreated (nSYY) groups, and conditioned media (CM-SYY and CM-nSYY, respectively) were collected. The hepatoma cell line, McA-RH7777 was cultured for 4 weeks with SYY, CM-SYY, and CM-nSYY, designated McA-SYY, McA-SYYCM and McA-nSYYCM. The invasiveness and metastatic capabilities were evaluated using Matrigel invasion assay in vitro and pulmonary metastasis in vivo. Matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, N-cadherin, and vimentin protein levels in McA-SYYCM and McA-nSYYCM were evaluated by Western blot. Cytokine levels in conditioned media were tested using enzyme-linked immunosorbent assay (ELISA).

Results

Matrigel invasion assay indicated that the number of McA-SYYCM cells passing through the basement membrane was less than in McA-nSYYCM cells (P < 0.01). Similar results were also observed in vivo for lung metastasis. McA-SYYCM cells showed less pulmonary metastasis capabilities than McA-nSYYCM cells (P < 0.001). The reduced expression of MMP-2 and reversed epithelial to mesenchymal transition with E-cadherin upregulation, and N-cadherin and vimentin downregulation were also found in McA-SYYCM compared to McA-nSYYCM. Metastasis-promoting cytokines hepatocyte growth factor, interleukin-6, transforming growth factor-β1, and vascular endothelial growth factor were markedly decreased in CM-SYY compared to CM-nSYY.

Conclusions

SYY attenuates hepatoma cell invasiveness and metastasis capabilities through downregulating cytokines secreted by activated hepatic stellate cells.

【 授权许可】

   
2013 Jia et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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