Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice
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摘要:
Objective:To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth in vivo and investigate the underlying mechanisms.Methods:A HCC xenograft mouse model was developed by producing with huh7 cells.After 5 days following xenograft implantation,ten HCC xenograft mice were given intra-gastric administration with 10 mg/(kg·d) dose of BBP or saline for 3 weeks.Tumor growth in HCC xenograft mice was evaluated by measuring the tumor weight and volume.Cell apoptosis,proliferation or tumor angiogenesis were examined via immunohistochemical (IHC) staining for transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL),proliferating cell nuclear antigen (PCNA) or cluster of differentiation 31 (CD31),respectively.Phosphorylation of signal transducer and activator of transcription 3 (STAT3) were determined by Westem blot.The mRNA and protein expressions of Bcl-2,Bax,Cyclin D1 and Cyclin-dependent kinase 4 (CDK4) in HCC tumor tissues were respectively determined by reverse transcription polymerase chain reaction (RT-PCR) and Westem blot.The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining.Results:BBP treatment led to a significant decrease on tumor volume and tumor weight in HCC mice (P<0.05) and had no effect on the change of body weight.In addition,BBP profoundly promoted cell apoptosis,inhibited cell proliferation and intratumoral microvessel density in HCC tumor tissues (P<0.05).Moreover,BBP treatment remarkably suppressed the STAT3 phosphorylation and modulated the expression of critical target genes including Bcl-2,Bax,Cyclin D1,CDK4 and VEGF-A in HCC mice.Conclusion:BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.