Inhibition of the signaling pathway of syndecan-1 by synstatin: A promising anti-integrin inhibitor of angiogenesis and proliferation in HCC in rats.

AIM OF WORK

The study was conducted for evaluation of the antitumor activity of SSTN against HCC induced by thioacetamide in rats.

METHODS

Sixty male Sprague-Dawley rats were randomized into four equal groups: Control, SSTN, HCC, and HCC + SSTN. Liver function tests were measured in serum. Liver homogenate was used for determination of: i) integrinαѴβ3 (ITGαѴβ3), insulin like growth factor-1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and alpha-fetoprotein (AFP) levels by ELISA, ii) syndecan-1 (CD-138), IGF-1R and VEGF genes expressions by qRT-PCR, iii) MDA, NO, GSH concentrations and SOD activity. Histopathological and immunohistochemical examination of liver tissue was performed.

RESULTS

SSTN decreased HCC-induced elevation in ALT, AST, ALP and GGT activities and reversed HCC-induced reduction in total protein and albumin concentrations significantly. SSTN significantly elevated hepatic SOD and GSH and reduced both NO and MDA levels. Protein levels of ITGαѴβ3, IGF-1R, VEGF, FGF-2 and AFP were decreased in HCC- SSTN group as well as gene expression of CD-138, IGF-1R and VEGF compared with HCC group.

CONCLUSIONS

SSTN down regulates ITGαѴβ3 receptor and subsequently reduces the activation of angiogenic growth factors VEGF and FGF-2. Therefore, SSTN is becoming a promising anti-integrin αѴβ3 that inhibits angiogenesis and proliferation in HCC.