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Article

Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway

  • Authors:
    • Jun Liao
    • Teng Xu
    • Jia-Xuan Zheng
    • Jiu-Mao Lin
    • Qiao-Yan Cai
    • De-Biao Yu
    • Jun Peng
  • View Affiliations / Copyright

    Affiliations: Department of Acupuncture and Moxibustion, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
  • Pages: 79-84
    |
    Published online on: April 22, 2013
       https://doi.org/10.3892/ijmm.2013.1358
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Abstract

Signal transducer and activator of transcription 3 (STAT3) is persistently activated in cancer cells and contributes to malignant progression in various types of cancer. The Janus-activated kinase (JAK) family phosphorylates STAT3 in response to stimulation by cytokines or growth factors. The JAK1-STAT3 signaling pathway plays an important role in cell proliferation and apoptosis. Nitidine chloride (NC) is a benzophenanthridine alkaloid that has been reported as an antitumor agent due to its its inhibitory effects on topoisomerase I. Using a mouse xenograft model of hepatocellular carcinoma (HCC), this study aimed to evaluate the effects of NC on tumor growth in vivo and to elucidate the underlying mechanisms. The analysis of the effects of NC on apoptosis in HCC tumor xenografts in mice was carried out by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay; the expression of Bcl-2, Bax, cyclin-dependent kinase (CDK)4, cyclin D1, p21 and proliferating cell nuclear antigen (PCNA) was analyzed by immunohistochemistry; and the protein expression of JAK1 and STAT3 was examined by western blot analysis. Our results revealed that treatment with NC decreased the tumor volume and tumor weight, suggesting that NC inhibits HCC cell growth in vivo. In addition, NC blocked the activation of JAK1-STAT3 in the tumor tissues, which in turn resulted in the induction of cancer cell apoptosis and the inhibition of proliferation. Consequently, treatment with NC downregulated the expression of cyclin D1, CDK4 and Bcl-2 and increased the level of p21 and Bax. Our data provide a molecular basis for the antitumor activity of NC.
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Copy and paste a formatted citation
Spandidos Publications style
Liao J, Xu T, Zheng J, Lin J, Cai Q, Yu D and Peng J: Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway. Int J Mol Med 32: 79-84, 2013.
APA
Liao, J., Xu, T., Zheng, J., Lin, J., Cai, Q., Yu, D., & Peng, J. (2013). Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway. International Journal of Molecular Medicine, 32, 79-84. https://doi.org/10.3892/ijmm.2013.1358
MLA
Liao, J., Xu, T., Zheng, J., Lin, J., Cai, Q., Yu, D., Peng, J."Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway". International Journal of Molecular Medicine 32.1 (2013): 79-84.
Chicago
Liao, J., Xu, T., Zheng, J., Lin, J., Cai, Q., Yu, D., Peng, J."Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway". International Journal of Molecular Medicine 32, no. 1 (2013): 79-84. https://doi.org/10.3892/ijmm.2013.1358
Copy and paste a formatted citation
x
Spandidos Publications style
Liao J, Xu T, Zheng J, Lin J, Cai Q, Yu D and Peng J: Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway. Int J Mol Med 32: 79-84, 2013.
APA
Liao, J., Xu, T., Zheng, J., Lin, J., Cai, Q., Yu, D., & Peng, J. (2013). Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway. International Journal of Molecular Medicine, 32, 79-84. https://doi.org/10.3892/ijmm.2013.1358
MLA
Liao, J., Xu, T., Zheng, J., Lin, J., Cai, Q., Yu, D., Peng, J."Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway". International Journal of Molecular Medicine 32.1 (2013): 79-84.
Chicago
Liao, J., Xu, T., Zheng, J., Lin, J., Cai, Q., Yu, D., Peng, J."Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway". International Journal of Molecular Medicine 32, no. 1 (2013): 79-84. https://doi.org/10.3892/ijmm.2013.1358
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