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C ompound A stragalus and S alvia miltiorrhiza extracts suppress hepatocarcinogenesis by modulating transforming growth factor‐β/ S mad signaling
Author(s) -
Hu Xiangpeng,
Rui Wenjuan,
Wu Chao,
He Shufang,
Jiang Jiemei,
Zhang Xiaoxiang,
Yang Yan
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12490
Subject(s) - mad2 , hepatocellular carcinoma , in vivo , transforming growth factor , medicine , activator (genetics) , cancer research , endocrinology , biology , receptor , cancer , cell cycle , microbiology and biotechnology , anaphase
Background and Aim Previous studies showed C ompound Astragalus and S alvia miltiorrhiza extract ( CASE ), extract from A stragalus membranaceus and S alvia miltiorhiza , significantly suppresses hepatocellular carcinoma ( HCC ) in rats induced by diethylinitrosamine ( DEN ), and in vitro experiments further demonstrated that CASE 's anti‐ H ep G 2 cell invasion is associated with transforming growth factor‐β ( TGF ‐β). We hypothesized that CASE 's suppression of HCC is modulated by TGF ‐β/ S mad signaling, and we conducted this in vivo study to test this hypothesis. Methods Rats were divided into the normal control, the DEN group, and three CASE (60, 120, and 240 mg/kg) treatment groups. The expression of phosphorylation(p) S mad both at C ‐terminal and linker region, plasminogen activator inhibitor 1, and S mad4 and S mad7 of liver tissues were measured and compared across the five groups. Results The positive staining of p S mad2 L and p S mad3 L increased both in hepatoma nodule areas and adjacent relatively normal liver tissues in rats treated with DEN , while the positive staining of p S mad2 C and p S mad3 C increased only in relatively normal liver tissues adjacent to hepatoma tissues. The elevated expression of p S mad2 C , p S mad2 L , p S mad3 L , S mad4, and plasminogen activator inhibitor 1 proteins were suppressed by CASE in a dose‐dependent manner. CASE treatment also significantly reduced the intranuclear amounts of p S mad2 L and p S mad3 L , and upregulated the elevation of p S mad3 C positive cells and protein expression in a dose‐dependent manner. Conclusion The results suggest tha t CASE significantly suppresses HCC progression by mediating TGF ‐β/ S mad signaling, especially by modulating S mad3 phosphorylation both at the C ‐terminal and linker region.