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Article

Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma

  • Authors:
    • Qian Sun
    • Ronghua Wang
    • Yan Wang
    • Jing Luo
    • Peng Wang
    • Bin Cheng
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
  • Pages: 933-939
    |
    Published online on: December 12, 2013
       https://doi.org/10.3892/or.2013.2917
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Abstract

Hepatocellular carcinoma (HCC) is a highly lethal cancer with increasing worldwide incidence, and there are few therapeutics options available for patients with HCC. Thus, novel therapeutic targets for this disease are desperately needed. Chronic infection with hepatitis B virus (HBV) is the major risk factor for the development of HCC, while hepatitis B virus X protein (HBx) is essential for HBV-associated HCC. Based on our previous studies showing that HBx promoted hepatocarcinogenesis of the human non-tumor hepatic cell line L02 and activated Notch1 signaling, Notch1 short hairpin RNA (shRNA) was utilized to inhibit Notch1 mRNA in the present study. We observed that Notch1 shRNA inhibited cell proliferation together with decreased activity of the Notch1 pathway in vitro, and also markedly suppressed tumor formation of L02/HBx cells in a BALB/c nude mouse model in vivo. Furthermore, the blockade of Notch1 was capable of arresting the cell cycle in the G0/G1 phase through the downregulation of CyclinD1, CDK4, E2F1 and the upregulation of p21 and Rb, while all of these factors were involved in the CyclinD1/CDK4 pathway. Inhibition of Notch1 by shRNA markedly promoted the apoptosis of L02/HBx cells via the caspase-9-caspase-3 pathway. These data suggest that inhibition of Notch1 impairs the growth of human HBx-transformed L02 cells, and Notch1 may be a putative therapeutic target for human HBx-associated HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Sun Q, Wang R, Wang Y, Luo J, Wang P and Cheng B: Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma. Oncol Rep 31: 933-939, 2014.
APA
Sun, Q., Wang, R., Wang, Y., Luo, J., Wang, P., & Cheng, B. (2014). Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma. Oncology Reports, 31, 933-939. https://doi.org/10.3892/or.2013.2917
MLA
Sun, Q., Wang, R., Wang, Y., Luo, J., Wang, P., Cheng, B."Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma". Oncology Reports 31.2 (2014): 933-939.
Chicago
Sun, Q., Wang, R., Wang, Y., Luo, J., Wang, P., Cheng, B."Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma". Oncology Reports 31, no. 2 (2014): 933-939. https://doi.org/10.3892/or.2013.2917
Copy and paste a formatted citation
x
Spandidos Publications style
Sun Q, Wang R, Wang Y, Luo J, Wang P and Cheng B: Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma. Oncol Rep 31: 933-939, 2014.
APA
Sun, Q., Wang, R., Wang, Y., Luo, J., Wang, P., & Cheng, B. (2014). Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma. Oncology Reports, 31, 933-939. https://doi.org/10.3892/or.2013.2917
MLA
Sun, Q., Wang, R., Wang, Y., Luo, J., Wang, P., Cheng, B."Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma". Oncology Reports 31.2 (2014): 933-939.
Chicago
Sun, Q., Wang, R., Wang, Y., Luo, J., Wang, P., Cheng, B."Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma". Oncology Reports 31, no. 2 (2014): 933-939. https://doi.org/10.3892/or.2013.2917
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