Skip to main content
SpringerLink
Log in

Diwu Yanggan Modulates the Wnt/β-catenin Pathway and Inhibits Liver Carcinogenesis Signaling in 2-AAF/PH Model Rats

  • Published:
Current Medical Science Aims and scope Submit manuscript

Summary

The activation of the Wnt/β-catenin signaling pathway in oval cells after liver injury is implicated in hepatocarcinogenesis. Diwu Yanggan capsule is a Chinese herbal medicine that has been used for treating liver disorder. The present study aimed to examine the mechanism by which Diwu Yanggan inhibits liver carcinogenesis, and the involvement of the Wnt/β-catenin signaling pathway. Diwu Yanggan capsule was administered to 2-acetaminofluorene/partial hepatectomy (2-AAF/PH) rats, a murine model of liver injury. The biomarkers of oval cells and key proteins in the Wnt/β-catenin signaling pathway were assessed on postoperative day 8, 10, 14, 17, 19 and 22. The results showed that treatment with Diwu Yanggan was associated with reduced expression of oval cell and stem cell biomarkers in the 2-AAF/PH animals. The expression pattern of key proteins in the Wnt/β-catenin pathway was altered in Diwu Yanggan-treated animals, indicating that the Diwu Yanggan treatment accelerated the activation of the Wnt/β-catenin pathway in the initial stage and contributed to its deactivation in the later stage. Histological findings indicated that hepatocyte proliferation was suppressed in Diwu Yanggan-treated animals, compared with untreated 2-AAF/PH animals. Taken together, Diwu Yanggan capsule may reduce the risk of hepatocarcinogenesis by modulating the Wnt/β-catenin signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jemal A, Ward EM, Johnson CJ, et al. Annual Report to the Nation on the Status of Cancer, 1975–2014, Featuring Survival. J Natl Cancer Inst, 2017,109(9), doi: https://doi.org/10.1093/jnci/djx030

    Google Scholar 

  2. Chen JG, Zhang SW. Liver cancer epidemic in China: past, present and future. Semin Cancer Biol, 2011,21(1):59–69

    Article  Google Scholar 

  3. Li YS, Leng CL, Chen MT, et al. Mouse hepatic neoplasm formation induced by trace level and low frequency exposure to diethylnitrosamine through beta-catenin signaling pathway. Toxicol Res, 2015,5(1):210–223

    Article  Google Scholar 

  4. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell, 2012,149(6):1192–1205

    Article  CAS  Google Scholar 

  5. Nejak-Bowen KN, Monga SP. Beta-catenin signaling, liver regeneration and hepatocellular cancer: sorting the good from the bad. Semin Cancer Biol, 2011,21(1):44–58

    Article  CAS  Google Scholar 

  6. Vilchez V, Turcios L, Marti F, et al. Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment. World J Gastroenterol, 2016,22(2):823–832

    Article  CAS  Google Scholar 

  7. Tien LT, Ito M, Nakao M, et al. Expression of beta-catenin in hepatocellular carcinoma. World J Gastroenterol, 2005,11(16):2398–2401

    Article  CAS  Google Scholar 

  8. Oh SH, Hatch HM, Petersen BE. Hepatic oval ‘stem’ cell in liver regeneration. Semin Cell Dev Biol, 2002,13(6):405–409

    Article  CAS  Google Scholar 

  9. Fausto N, Campbell JS. The role of hepatocytes and oval cells in liver regeneration and repopulation. Mech Dev, 2003,120(1):117–130

    Article  CAS  Google Scholar 

  10. Sell S, Dunsford HA. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol, 1989,134(6):1347–1363

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang B, Jacob ST. Role of cancer stem cells in hepatocarcinogenesis. Genome Med, 2011,3(2):11

    Article  CAS  Google Scholar 

  12. Tatematsu M, Ho RH, Kaku T, et al. Studies on the proliferation and fate of oval cells in the liver of rats treated with 2-acetylaminofluorene and partial hepatectomy. Am J Pathol, 1984,114(3):418–430

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang JR. Analyses of liver cancer risk reduction in patients with chronic hepatitis B by treatment with Diwu Yanggan capsule with a liver cancer predictive model. Hubei Univ Chin Med (Chinese), 2014.

  14. Ye ZH. The effects and mechanisms of diwu yanggan capsule on hepatocarcinogenesis in the Solt-Farber model of liver cancer. Hubei University of Chinese Medicine (Chinese), 2015.

  15. Li HM, Zhao BB, Xiang G, et al. Tonifying Kidney Network to Modulate Liver Regeneration Microenvironment to Prevent and Cure Liver Cancer. J Hubei Univ Chin Med (Chinese), 2015,17(01):5–8

    CAS  Google Scholar 

  16. Li HM. Construction and application of tertiary prevention program for liver cancer based on “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment”. Chin J Integr Tradit West Med Liver Dis (Chinese), 2015,25(06):369–372

    Google Scholar 

  17. Zhao BB, Li HM, Gao X, et al. The Herbal Compound “Diwu Yanggan” Modulates Liver Regeneration by Affecting the Hepatic Stem Cell Microenvironment in 2-Acetylaminofluorene/Partial Hepatectomy Rats. Evid Based Complementary Altern Med, 2015,2015:1–7

    Google Scholar 

  18. Alison M, Golding M, Lalani E-N, et al. Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells. J Hepatol, 1997,26(2):343–352

    Article  CAS  Google Scholar 

  19. Xiang S, Dong HH, Liang HF, et al. Oval cell response is attenuated by depletion of liver resident macrophages in the 2-AAF/partial hepatectomy rat. PLoS One, 2012,7(4):e35180

    Article  CAS  Google Scholar 

  20. Nhieu JTV, Renard CA, Wei Y, et al. Nuclear Accumulation of Mutated β-Catenin in Hepatocellular Carcinoma Is Associated with Increased Cell Proliferation. Am J Pathol, 1999,155(3):703–710

    Article  CAS  Google Scholar 

  21. Nambotin SB, Wands JR, Kim M. Points of therapeutic intervention along the Wnt signaling pathway in hepatocellular carcinoma. Anticancer Agents Med Chem, 2011,11(6):549–559

    Article  CAS  Google Scholar 

  22. Gedaly R, Galuppo R, Daily MF, et al. Targeting the Wnt/β-Catenin Signaling Pathway in Liver Cancer Stem Cells and Hepatocellular Carcinoma Cell Lines with FH535. PLoS One, 2014,9(6):e99272

    Article  Google Scholar 

  23. Xia S, Guo Z, Xu X, et al. Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells, maintaining liver tolerance. Blood, 2008,112(8):3175–3185

    Article  CAS  Google Scholar 

  24. Tahmasebi Birgani M, Carloni V. Tumor Microenvironment, a Paradigm in Hepatocellular Carcinoma Progression and Therapy. Int J Mol Sci, 2017,18(2):e405

    Article  Google Scholar 

  25. Leonardi GC, Candido S, Cervello M, et al. The tumor microenvironment in hepatocellular carcinoma (review). Int J Oncol, 2012,40(6):1733–1747

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Both authors contributed equally to this work.

Authors and Affiliations

  1. Basic Medicine College, Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China

    Bin-bin Zhao

  2. Hepatology Institute, Hubei Provincial Hospital of Traditional Chinese Medicine & Affiliated Hospital to Hubei University of Traditional Chinese Medicine, Hubei Institute of Traditional Chinese Medicine, Wuhan, 430061, China

    Zhi-hua Ye, Xiang Gao & Han-min Li

Authors
  1. Bin-bin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-hua Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Han-min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Han-min Li.

Additional information

Conflict of Interest Statement

The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

This work was supported by the National Natural Science Foundation of China (Nos. 81703973, 81973669, 81703912, and 81603484), National Key R&D Program of China (No. 2018YFC1705600), Research Projects of Key Disease for Practice Development of National TCM Clinical Research Bases (No. JDZX2015172), Science and Technology Research Program of Hubei Education Department for Young Investigators (No. Q20172003), The Green Seedlings Program of Hubei University of Chinese Medicine (No. HUCM[2016]224), Special Program for Advanced Researchers of Hubei University of Chinese Medicine (No. 5114-100724), and Li Han-min National Famous Old Chinese Medicine Experts Inheritance Studio.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Bb., Ye, Zh., Gao, X. et al. Diwu Yanggan Modulates the Wnt/β-catenin Pathway and Inhibits Liver Carcinogenesis Signaling in 2-AAF/PH Model Rats. CURR MED SCI 39, 913–919 (2019). https://doi.org/10.1007/s11596-019-2123-2

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-019-2123-2

Key words

Search

Navigation