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World Journal of Surgery

, Volume 37, Issue 7, pp 1688–1694 | Cite as

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

  • Xiao Du
  • Yu-Pei ZhaoEmail author
  • Tai-Ping Zhang
  • Li Zhou
  • Ge Chen
  • Quan-Cai Cui
  • Jie Shi
  • Tian-Xiao Wang
  • Lei You
  • Hong Shu
Article

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.

Keywords

Overall Survival Pancreatic Cancer Gemcitabine Pancreatic Cancer Cell Notch Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

268_2013_2010_MOESM1_ESM.tif (208 kb)
Fig. S1 Impacts of Notch1 siRNA on growth inhibition in 3 cell lines. Supplementary material 1 (TIFF 208 kb)

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Copyright information

© Société Internationale de Chirurgie 2013

Authors and Affiliations

  • Xiao Du
    • 1
  • Yu-Pei Zhao
    • 1
    Email author
  • Tai-Ping Zhang
    • 1
  • Li Zhou
    • 1
  • Ge Chen
    • 1
  • Quan-Cai Cui
    • 2
  • Jie Shi
    • 2
  • Tian-Xiao Wang
    • 1
  • Lei You
    • 1
  • Hong Shu
    • 1
  1. 1.Department of General SurgeryPeking Union Medical College Hospital, National Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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