title: Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer cells.
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.
authors: Institute of Bioinformatics and Structural Biology & Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors: Yi-Wen
authors: YW
authors: Chen
authors: Jieh-Yuan
authors: JY
authors: Liu
authors: Szu-Ting
authors: ST
authors: Lin
authors: Ji-Min
authors: JM
authors: Li
authors: Shun-Hong
authors: SH
authors: Huang
authors: Jing-Yi
authors: JY
authors: Chen
authors: Jing-Yiing
authors: JY
authors: Wu
authors: Cheng-Chin
authors: CC
authors: Kuo
authors: Chieh-Lin
authors: CL
authors: Wu
authors: Ying-Chieh
authors: YC
authors: Lu
authors: You-Hsuan
authors: YH
authors: Chen
authors: Chiao-Yuan
authors: CY
authors: Fan
authors: Ping-Chun
authors: PC
authors: Huang
authors: Ching-Hsuan
authors: CH
authors: Law
authors: Ping-Chiang
authors: PC
authors: Lyu
authors: Hsiu-Chuan
authors: HC
authors: Chou
authors: Hong-Lin
authors: HL
authors: Chan
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms; D025941:Protein Interaction Mapping; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D057825:Two-Dimensional Difference Gel Electrophoresis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D020543:Proteome; D003841:Deoxycytidine; D000093542:Gemcitabine