Issue 11, 2011
From the journal:

Molecular BioSystems

Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer cells†

Yi-Wen Chen,a   Jieh-Yuan Liu,b   Szu-Ting Lin,a   Ji-Min Li,a   Shun-Hong Huang,a   Jing-Yi Chen,c   Jing-Yiing Wu,ad   Cheng-Chin Kuo,d   Chieh-Lin Wu,a   Ying-Chieh Lu,a   You-Hsuan Chen,a   Chiao-Yuan Fan,a   Ping-Chun Huang,a   Ching-Hsuan Law,a   Ping-Chiang Lyu,*a   Hsiu-Chuan Chou*c  and  Hong-Lin Chan*a  

* Corresponding authors

a Institute of Bioinformatics and Structural Biology & Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan
E-mail: pclyu@mx.nthu.edu.tw, hlchan@life.nthu.edu.tw
Fax: +886-3-5715934
Tel: +886-3-5742762

b National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Miaoli 350, Taiwan

c Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan
E-mail: chouhc@mail.nhcue.edu.tw
Fax: +886-3-5257178
Tel: +886-3-5213132ext2721

d Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan

Abstract

Currently, the most effective agent against pancreatic cancer is gemcitabine (GEM), which inhibits tumor growth by interfering with DNA replication and blocking DNA synthesis. However, GEM-induced drug resistance in pancreatic cancer compromises the therapeutic efficacy of GEM. To investigate the molecular mechanisms associated with GEM-induced resistance, 2D-DIGE and MALDI-TOF mass spectrometry were performed to compare the proteomic alterations of a panel of differential GEM-resistant PANC-1 cells with GEM-sensitive pancreatic cells. The proteomic results demonstrated that 33 proteins were differentially expressed between GEM-sensitive and GEM-resistant pancreatic cells. Of these, 22 proteins were shown to be resistance-specific and dose-dependent in the regulation of GEM. Proteomic analysis also revealed that proteins involved in biosynthesis and detoxification are significantly over-expressed in GEM-resistant PANC-1 cells. In contrast, proteins involved in vascular transport, bimolecular decomposition, and calcium-dependent signal regulation are significantly over-expressed in GEM-sensitive PANC-1 cells. Notably, both protein–protein interaction of the identified proteins with bioinformatic analysis and immunoblotting results showed that the GEM-induced pancreatic cell resistance might interplay with tumor suppressor protein p53. Our approach has been shown here to be useful for confidently detecting pancreatic proteins with differential resistance to GEM. Such proteins may be functionally involved in the mechanism of chemotherapy-induced resistance.

Graphical abstract: Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer cells

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Article information

DOI
https://doi.org/10.1039/C1MB05125C
Article type
Paper
Submitted
30 Mar 2011
Accepted
16 Aug 2011
First published
06 Sep 2011

Mol. BioSyst., 2011,7, 3065-3074

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Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer cells

Y. Chen, J. Liu, S. Lin, J. Li, S. Huang, J. Chen, J. Wu, C. Kuo, C. Wu, Y. Lu, Y. Chen, C. Fan, P. Huang, C. Law, P. Lyu, H. Chou and H. Chan, Mol. BioSyst., 2011, 7, 3065 DOI: 10.1039/C1MB05125C

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