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Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 6, pp 1055–1064 | Cite as

Inducing apoptosis and enhancing chemosensitivity to Gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell

  • San-Hua Wei
  • Ke Dong
  • Fang Lin
  • Xi Wang
  • Bin Li
  • Jian-jun Shen
  • Qing Zhang
  • Rui Wang
  • Hui-Zhong ZhangEmail author
Original Article

Abstract

Purpose

Resistance to chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic carcinoma. Myeloid cell leukemia-1 (Mcl-1) is highly up-regulated in pancreatic carcinoma and is associated with the anti-apoptosis and the resistance to chemotherapy drugs. Suppression of Mcl-1 would be an approach to induce apoptosis and enhance the chemosensitivity.

Methods

In this study, three pancreatic cancer cell lines (PANC-1, BxPC-3 and SW1900) stably expressing shRNAs targeting Mcl-1 gene were established and gene expression inhibition was assessed by Real-Time QPCR and Western blotting. The effects of Mcl-1 downregulation mediated by RNAi were explored in vitro and in vivo.

Results

We showed that the specific downregulation of Mcl-1 strikingly inhibited cell growth, colony formation, cell cycle arrest and induced apoptosis in pancreatic cancer cells in vitro, and markedly decreased the tumorigenicity in a mouse xenograft model. Moreover, knockdown of Mcl-1 significantly increased the chemosensitivity to Gemcitabine in pancreatic carcinoma cells.

Conclusions

Our data suggests that the specific downregulation of Mcl-1 by RNAi is a promising approach to induce apoptosis and enhance the chemosensitivity for pancreatic carcinoma gene therapy.

Keywords

Mcl-1 RNA interference Apoptosis Pancreatic carcinoma Chemotherapy 

Notes

Acknowledgments

The research was supported by a grant from the Natural Science Foundation of Shaanxi Province (2003K10G44). Thanks to every one of department of clinical laboratory for their sincere help and technical support.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • San-Hua Wei
    • 1
  • Ke Dong
    • 2
  • Fang Lin
    • 1
  • Xi Wang
    • 1
  • Bin Li
    • 2
  • Jian-jun Shen
    • 2
  • Qing Zhang
    • 2
  • Rui Wang
    • 1
  • Hui-Zhong Zhang
    • 1
    • 2
    Email author
  1. 1.Research Center, Tangdu HospitalFourth Military Medical UniversityXi’anChina
  2. 2.Department of Clinical Diagnosis, Tangdu HospitalFourth Military Medical UniversityXi’anChina

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