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Article

Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo

  • Authors:
    • Ya-Dong Dong
    • Long Cui
    • Cheng-Hong Peng
    • Dong-Feng Cheng
    • Bao-San Han
    • Fang Huang
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
  • Pages: 87-94
    |
    Published online on: October 4, 2012
       https://doi.org/10.3892/or.2012.2070
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Abstract

The high-mobility group box 1 (HMGB1) signaling pathway plays a crucial role in tumorigenesis and progression of many malignant cancers. The present study aimed to investigate the expression and clinical significance of HMGB1 in human primary liver cancer, and further explore the molecular mechanisms of HMGB1 in tumor growth and metastasis. Forty cases of human liver cancer and normal liver tissues were collected. The expression of HMGB1 was assessed using RT-PCR and western blot assays in biopsy samples. The HMGB1 pathway in vitro was blocked using transfection of the recombinant small hairpin RNA adenovirus vector rAd5-HMGB1 into the human liver cancer cell line SMMC-7721. The expression of HMGB1, phosphorylated AKT (p-AKT), Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by Real-PCR and western blot assays. Cell proliferative activities and metastatic capability were determined by MTT and Transwell assays. Cell cycle distribution and apoptosis were detected by flow cytometry. A subcutaneous xenograft tumor model was established, validating the effects of rAd5-HMGB1 on tumor growth in vivo. As a consequence, HMGB1 was found to be highly expressed in liver cancer compared with normal tissues, and was positively associated with pathological grade and distant metastases of liver cancer. Knockdown of HMGB1 downregulated the expression of p-AKT, Ki-67 and MMP-2, inhibited the proliferative activities and metastatic potential of SMMC-7721 cells, induced cell cycle arrest and apoptosis, and slowed the growth of xenograft tumors. Altogether, the expression of HMGB1 is closely correlated with pathological grade and distant metastases of liver cancer, and knockdown of HMGB1 inhibits liver cancer growth and metastasis, suggesting that HMGB1 may be involved in liver cancer development and progression through AKT-mediated regulation of Ki-67 and MMP-2 expression, and represent a potential therapeutic target for this aggressive malignancy.
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Copy and paste a formatted citation
Spandidos Publications style
Dong Y, Cui L, Peng C, Cheng D, Han B and Huang F: Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep 29: 87-94, 2013.
APA
Dong, Y., Cui, L., Peng, C., Cheng, D., Han, B., & Huang, F. (2013). Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncology Reports, 29, 87-94. https://doi.org/10.3892/or.2012.2070
MLA
Dong, Y., Cui, L., Peng, C., Cheng, D., Han, B., Huang, F."Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo". Oncology Reports 29.1 (2013): 87-94.
Chicago
Dong, Y., Cui, L., Peng, C., Cheng, D., Han, B., Huang, F."Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo". Oncology Reports 29, no. 1 (2013): 87-94. https://doi.org/10.3892/or.2012.2070
Copy and paste a formatted citation
x
Spandidos Publications style
Dong Y, Cui L, Peng C, Cheng D, Han B and Huang F: Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep 29: 87-94, 2013.
APA
Dong, Y., Cui, L., Peng, C., Cheng, D., Han, B., & Huang, F. (2013). Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncology Reports, 29, 87-94. https://doi.org/10.3892/or.2012.2070
MLA
Dong, Y., Cui, L., Peng, C., Cheng, D., Han, B., Huang, F."Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo". Oncology Reports 29.1 (2013): 87-94.
Chicago
Dong, Y., Cui, L., Peng, C., Cheng, D., Han, B., Huang, F."Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo". Oncology Reports 29, no. 1 (2013): 87-94. https://doi.org/10.3892/or.2012.2070
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