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Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice

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Abstract

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 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

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.

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Authors and Affiliations

  1. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    Hong-wei Chen, A-ling Shen, Jun Peng & Jian-feng Chu

  2. Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    Li-ya Liu, Jun Peng & Jian-feng Chu

Authors
  1. Hong-wei Chen
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  2. A-ling Shen
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  3. Li-ya Liu
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  4. Jun Peng
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  5. Jian-feng Chu
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Contributions

Chu JF, Peng J, Shen AL and Liu LY designed the research; Shen AL, Liu LY and Chen HW performed the research; Chu JF, Shen AL, Liu LY and Chen HW analyzed the data; and Chen HW, Shen AL and Liu LY wrote the paper.

Corresponding author

Correspondence to Jian-feng Chu.

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The authors declare no financial or commercial conflict of interest.

Additional information

Supported by the Developmental Fund of CHEN Ke-ji Integrative Medicine (No. CKJ2013009)

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Chen, Hw., Shen, Al., Liu, Ly. et al. Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice. Chin. J. Integr. Med. 26, 370–374 (2020). https://doi.org/10.1007/s11655-019-3010-1

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  • DOI: https://doi.org/10.1007/s11655-019-3010-1

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