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Notch1 Contributes to Chemoresistance to Gemcitabine and Serves as an Unfavorable Prognostic Indicator in Pancreatic Cancer

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Abstract

Background

Pancreatic cancer (PC) carries frequent chemoresistance and extremely dismal prognosis. The underlying mechanisms remain to be further elucidated. We here report the role of Notch1 in gemcitabine resistance and its prognostic significance in PC.

Methods

A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2), followed by examination of chemosensitivity to gemcitabine. On the other hand, Notch1 expression was evaluated immunohistochemically and correlated with clinicopathological and prognostic variables.

Results

Successful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. Immunohistochemical staining revealed that Notch1 was highly expressed in PC tissues (54.8 %), in contrast to that in para-tumor tissues (16.4 %). In addition, Notch1 positivity was significantly correlated with early-term metastasis and shortened overall survival. Multivariate Cox regression identified Notch1 as an independent prognostic factor.

Conclusions

Notch1 contributes to chemoresistance to gemcitabine, and serves as a significant indicator of unfavorable prognosis in PC.

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Authors and Affiliations

  1. Department of General Surgery, Peking Union Medical College Hospital, National Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Xiao Du, Yu-Pei Zhao, Tai-Ping Zhang, Li Zhou, Ge Chen, Tian-Xiao Wang, Lei You & Hong Shu

  2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Quan-Cai Cui & Jie Shi

Authors
  1. Xiao Du
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  2. Yu-Pei Zhao
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  3. Tai-Ping Zhang
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  4. Li Zhou
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  5. Ge Chen
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  6. Quan-Cai Cui
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  7. Jie Shi
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  8. Tian-Xiao Wang
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  9. Lei You
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  10. Hong Shu
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Corresponding author

Correspondence to Yu-Pei Zhao.

Additional information

The study was supported by National Natural Science Foundation (81071693) and National Laboratory of Molecular Biology Special Foundation (2060204), China.

Electronic supplementary material

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Fig. S1

Impacts of Notch1 siRNA on growth inhibition in 3 cell lines. Supplementary material 1 (TIFF 208 kb)

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Du, X., Zhao, YP., Zhang, TP. et al. Notch1 Contributes to Chemoresistance to Gemcitabine and Serves as an Unfavorable Prognostic Indicator in Pancreatic Cancer. World J Surg 37, 1688–1694 (2013). https://doi.org/10.1007/s00268-013-2010-0

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  • DOI: https://doi.org/10.1007/s00268-013-2010-0

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