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The herbal compound Songyou Yin (SYY) inhibits hepatocellular carcinoma growth and improves survival in models of chronic fibrosis via paracrine inhibition of activated hepatic stellate cells.
- Source :
-
Oncotarget [Oncotarget] 2015 Nov 24; Vol. 6 (37), pp. 40068-80. - Publication Year :
- 2015
-
Abstract
- Chronic fibrosis is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathological progression of hepatic fibrosis has been linked to cellular processes that promote tumor growth and metastasis. Several recent studies have highlighted the cross-talk between tumor cells and activated hepatic stellate cells (aHSCs) in HCC. The herbal compound Songyou Yin (SYY) is known to attenuate hepatoma cell invasion and metastasis via down-regulation of cytokine secretion by aHSCs. However the underlying mechanism of SYY treatment in reversal of hepatic fibrosis and metastasis of liver cancers is not known. In the current study, a nude mouse model with liver fibrosis bearing orthotopic xenograft was established and we found that SYY could reduce associated fibrosis, inhibit tumor growth and improve survival. In the subcutaneous tumor model with fibrosis, we found that SYY could inhibit liver cancer. In vitro, hepatoma cells incubated with conditioned media (CM) from SYY treated aHSCs showed reduced proliferation, decrease in colony formation and invasive potential. SYY treated group showed altered gene expression, with 1205 genes up-regulated and 1323 genes down-regulated. Gene cluster analysis indicated that phosphatidylinositol-3-kinase (PI3K) was one of the key genes altered in the expression profiles. PI3K related markers were all significantly down-regulated. ELISA also indicated decreased secretion of cytokines which were regulated by PI3K/AKT signaling after SYY treatment in the hepatic stellate cell line, LX2. These data clearly demonstrate that SYY therapy inhibits HCC invasive and metastatic potential and improves survival in nude mice models with chronic fibrosis background via inhibition of cytokine secretion by activated hepatic stellate cells.
- Subjects :
- Animals
Blotting, Western
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Cell Line
Cell Line, Tumor
Chronic Disease
Cytokines genetics
Cytokines metabolism
Gene Expression Regulation, Neoplastic drug effects
Hepatic Stellate Cells metabolism
Humans
Liver Cirrhosis genetics
Liver Cirrhosis metabolism
Liver Neoplasms genetics
Liver Neoplasms metabolism
Male
Mice, Inbred BALB C
Mice, Nude
Paracrine Communication drug effects
Paracrine Communication genetics
Phosphatidylinositol 3-Kinases genetics
Phosphatidylinositol 3-Kinases metabolism
Phytotherapy methods
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction drug effects
Signal Transduction genetics
Survival Analysis
Tumor Burden drug effects
Tumor Burden genetics
Xenograft Model Antitumor Assays
Carcinoma, Hepatocellular prevention & control
Drugs, Chinese Herbal pharmacology
Hepatic Stellate Cells drug effects
Liver Cirrhosis drug therapy
Liver Neoplasms prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26517671
- Full Text :
- https://doi.org/10.18632/oncotarget.5313