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Insulin-Like Growth Factor 1 Receptor Promotes the Growth and Chemoresistance of Pancreatic Cancer

Digestive Diseases and Sciences volume 58, pages 2705–2712 (2013)Cite this article

Abstract

Background

Insulin-like growth factor 1 receptor (IGF1R) plays important roles in the progression of pancreatic cancer. However, the underlying mechanism remains unclear.

Aims

The purpose of this study was to investigate the effects of IGF1R knockdown on the proliferation, apoptosis and chemosensitivity of pancreatic cancer cells, and explore the possible mechanisms.

Methods

Pancreatic cancer cells expressing IGF1R shRNA were established, and the cell proliferation, colony formation, and chemosensitivity to gemcitabine were examined in vitro. The activation of AKT and NF-κB was detected by Western blot analysis and luciferase assay, respectively. Xenograft mice models were established to evaluate the in vivo anti-tumor effects of IGF1R knockdown.

Results

IGF1R knockdown notably inhibited pancreatic cancer cell proliferation and colony formation, induced apoptosis, and inhibited xenograft tumor growth. Moreover, IGF1R knockdown significantly enhanced chemosensitivity to gemcitabine in pancreatic cancer cells, and this was correlated with the inhibition of PI3K/AKT and NF-κB pathways.

Conclusions

IGF1R knockdown suppresses tumor growth and enhances chemosensitivity in pancreatic cancer via the inhibition of PI3K/AKT and NF-κB pathways, and is a promising approach to overcome the chemoresistance of pancreatic cancer.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81172184) and Beijing Natural Science Foundation (No.7122188), and the Overseas Study Program of the China Scholarship Council, Beijing, China. We thank Professor Zebin Mao at the Department of Biochemistry and Molecular Biology in Health Science Center, Peking University for his assistance and technical support.

Conflict of interest

None.

Author information

Affiliations

  1. Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China

    Xiaodong Tian, Kun Hao, Changfu Qin, Kun Xie, Xuehai Xie & Yinmo Yang

Authors
  1. Xiaodong Tian
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  2. Kun Hao
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  3. Changfu Qin
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  4. Kun Xie
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  5. Xuehai Xie
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  6. Yinmo Yang
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Corresponding author

Correspondence to Yinmo Yang.

Additional information

Xiaodong Tian and Kun Hao contributed equally to this work.

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Tian, X., Hao, K., Qin, C. et al. Insulin-Like Growth Factor 1 Receptor Promotes the Growth and Chemoresistance of Pancreatic Cancer. Dig Dis Sci 58, 2705–2712 (2013). https://doi.org/10.1007/s10620-013-2673-2

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  • DOI: https://doi.org/10.1007/s10620-013-2673-2

Keywords

  • Chemosensitivity
  • Gemcitabine
  • Insulin-like growth factor 1 receptor
  • Pancreatic cancer