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Long-term interferon-α treatment suppresses tumor growth but promotes metastasis capacity in hepatocellular carcinoma

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To elucidate the effect of IFN-α treatment on tumor growth and metastasis of hepatocellular carcinoma (HCC).

Methods

IFN-α administration was conducted in nude mice using an orthotopic implantation model of human HCC, and the key molecular markers in the IFN-α treatment was detected by immunohistochemistry staining and PCR array.

Results

Up to 12 weeks of IFN-α treatment significantly suppressed tumor growth of HCC, but relatively increased the number of circulating tumor cells, which might be due to the enhanced tumor hypoxia as well as up-regulation of metastasis-related genes, such as HIF-1α, c-met, u-PA, PDGF-A, and IL-8. However, IFN-α had no direct effect on migration and invasion of HCC cells.

Conclusions

IFN-α has janus face of consistently suppressing HCC growth, however, promoting tumor metastasis capacity, which is of clinical indication for the scientific administration of IFN-α and the similar antiangiogenesis drugs for their dual effect on tumor growth and metastasis.

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Abbreviations

CTCs:

Circulating tumor cells.

ECGS:

Endothelial cell growth supplement

ECM:

Endothelial cell medium

FACS:

Fluorescence-activated cell sorting

HCC:

Hepatocellular carcinoma

IOD:

Integrated optical density

NS:

Normal saline

RFP:

Red-fluorescent protein

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Acknowledgments

This study was jointly supported by National Natural Science Foundation of China and the Research Grants Council (No. 30610301, 30872504), “211” Project for Higher Education (211xk24-1), and National key science & technology specific project (2008ZX10002-019, 021).

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Authors and Affiliations

  1. Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

    Peng-Yuan Zhuang

  2. Liver Cancer Institute and Zhongshan Hospital, Fudan University, 200032, Shanghai, People’s Republic of China

    Peng-Yuan Zhuang, Ju-Bo Zhang, Wei Zhang, Xiao-Dong Zhu, Ying Liang, Hua-Xiang Xu, Yu-Quan Xiong, Ling-Qun Kong, Lu Wang, Wei-Zhong Wu, Zhao-You Tang, Lun-Xiu Qin & Hui-Chuan Sun

  3. Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Guangxi, People’s Republic of China

    Ying Liang

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  1. Peng-Yuan Zhuang
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Correspondence to Lun-Xiu Qin or Hui-Chuan Sun.

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Zhuang, PY., Zhang, JB., Zhang, W. et al. Long-term interferon-α treatment suppresses tumor growth but promotes metastasis capacity in hepatocellular carcinoma. J Cancer Res Clin Oncol 136, 1891–1900 (2010). https://doi.org/10.1007/s00432-010-0848-1

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  • DOI: https://doi.org/10.1007/s00432-010-0848-1

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