Objective:

2

To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth

in vivo

and investigate the underlying mechanisms.

Methods:

2

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 Western 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 Western blot. The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining.

Results:

2

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:

2

BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.