FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo

Authors

  • Feng Fang MD,

    1. Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha City, People's Republic of China
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  • Lianyue Yang MD, PhD,

    Corresponding author
    1. Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha City, People's Republic of China
    • Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, People's Republic of China

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    • Fax: (011) 86-731-85533525

  • Yiming Tao MD,

    1. Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha City, People's Republic of China
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  • Wei Qin MD

    1. Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha City, People's Republic of China
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Abstract

BACKGROUND:

The so-called factor that binds to inducer of short transcripts-1 (FBI-1) purportedly plays an important role in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) remains unknown. The objective of this study was to investigate the expression level, clinical relevance, and biologic function of FBI-1 in HCC.

METHODS:

Real-time quantitative reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of FBI-1 and to analyze its relation to clinicopathologic parameters and to the prognosis of patients with HCC. In addition, the biologic functions of FBI-1 in regulating cell proliferation, migration, and reaction to chemotherapy were detected by using HepG2 cells and SMMC-7721 cells; subsequently, the molecular mechanism of FBI-1 also was investigated. Finally, a xenograft mouse model was used to validate the observations obtained from in vitro studies.

RESULTS:

Expression levels of FBI-1 messenger RNA and protein were elevated significantly in HCC tissues compared with adjacent nontumorous liver tissues (ANLTs). Increased FBI-1 expression was correlated with multiple tumor nodes, Edmondson-Steiner grade, and a poor prognosis in patients with HCC (P < .05). In vitro studies revealed that FBI-1 was capable of promoting cell proliferation (but not cell migration) by regulating the cell cycle regulation proteins p53, p21, and p27. In addition, FBI-1 could inhibit cell death induced by 5-fluorouracil or doxorubicin through suppressing the activation of p53. Consistent with the in vitro data, FBI-1 was capable of promoting cell proliferation and enhancing chemotherapy resistance of HCC in vivo.

CONCLUSIONS:

The current findings indicated that FBI-1 plays an important role in HCC carcinogenesis and chemotherapy tolerance, and FBI-1 may served as a novel prognostic marker and therapeutic target for HCC. Cancer 2012;. © 2011 American Cancer Society.

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