ABSTRACT
Objective:To study the effect of Biejia Jianwan on expressions of signal molecules and target genes of transforming growth factor-β (TGF-β)/Smad pathway in diethylnitrosamine (DEN)-induced rat hepatocellular carcinoma, and explore the mechanisms of Biejia Jianwan suppressing the invasion of hepatocellular carcinoma. Method:The rats were divided into three group, namely normal group, model group and Biejia Jianwan group (2.2 g·kg-1·d-1). Rats in Biejia Jianwan group and model group received intraperitoneal injections of DEN to induce sequential chronic inflammation, cirrhosis and hepatocellular carcinoma. At the sign of cirrhosis, rats in Biejia Jianwan group began taking Biejia Jianwan by gavage for 6 weeks. Rat blood was collected to measure serum levels of biochemical markers of liver function tests, including alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), albumin(Alb), γ-glutamyl transpeptadase(GGT), alkaline phosphatase(ALP). Rat livers were fixed in formalin and stained with hematoxylin-eosin (HE)staining， quantitative real-time PCR was used to test the mRNA expressions of TGF-β1， and Western blot was used to test protein expressions of TGF-β1, Smad2/3, p-Smad2/3, N-cadherin, E-cadherin and Vimentin. Result:All of the levels of biochemical markers showed no difference in Biejia Jianwan group and model group. Biejia Jianwan could improve the pathological changes of balloon-like degeneration, edema, and necrosis in liver cancer tissues. Importantly, the treatment dramatically decreased the mRNA expression of TGF-β1(P<0.01), and the protein expressions of TGF-β1, p-Smad2(P<0.01). Besides, the protein expression of N-cadherin and Vimentin were decreased significantly (P<0.01). Conclusion:Biejia Jianwan can inhibit epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cells activated via TGF-β/Smad pathway by reducing TGF-β1 expression, so as to suppress the metastasis and invasion of hepatocellular carcinoma.
ABSTRACT
Objective: To explore the therapeutic effect of licochalcone A (Lico A) on pulmonary fibrosis (PF). Method: Thirty mice were divided into five group, namely sham, model, Lico A (15, 30 mg·kg-1) and pirfenidone (300 mg·kg-1) groups. All of the groups except for sham group were intratracheally given bleomycin (BLM, 5 mg·kg-1). The sham group was given normal saline. On day 2, the mice were treated with Lico A and pirfenidone, respectively. On day 28, all of the mice were put to death. Then, lung tissues were collected and weighted. Pathological changes in lung tissue were measured by htoxylin eosin(HE) and Masson staining. The α-smooth muscle actin(α-SMA), Collagen I, fibronectin p-Smad2/3 and Smad2/3 were analyzed by Western blot. Then, transforming growth factor-β1 (TGF-β1)-induced MRC-5 cells were employed for evaluating the inhibitory activity of Lico A in vitro. Result: Compared with normal group, several pathological changes, including alveolar space collapse, emphysema, infiltration of inflammatory cells, and collagen deposition were observed in the BLM-treated mice, and these pathological changes were markedly attenuated by subsequent treatment with Lico A. Lico A could significantly inhibit BLM-induced up-regulation of α-SMA and Collagen I and phosphorylation of Smad2/3 in lung tissues of mice(PPβ-induced α-SMA and fibronectin expression in MRC-5 cells(PPConclusion: The preliminary mechanisms of the anti-fibrosis effect of Lico A may inhibit TGF-β/Smad pathway.