Targeting to overexpressed glucose-regulated protein 78 in gastric cancer discovered by 2D DIGE improves the diagnostic and therapeutic efficacy of micelles-mediated system

Chun Chia Cheng, Norman Lu, Cheng Liang Peng, Chun Chao Chang, Fu Der Mai, Ling Yun Chen, Mei Hsiu Liao, Wen Ming Wang, Jungshan Chang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The survivals of gastric cancer (GC) patients are associated with early diagnosis and effective treatments. Therefore, it is urgent for the discovery of early GC biomarkers and tumor-targeting therapeutics. The aim of this study was to uncover putative tissue biomarkers of GC using 2D DIGE and then apply one of these specific markers in GC treatment. We found three putative biomarkers of GC with significant differences in expression level compared to adjacent normal tissue, including glucose-regulated protein 78 (GRP78) and glutathione s-transferase pi (GSTpi) with increased expression level, and alpha-1 antitrypsin (A1AT) with reduced expression level. The overexpressed GRP78 was used as a targeted protein for guiding the drugs to tumor cells, leading to more effective treatment for GC xenografts. Our results demonstrated that the designated GRP78-binding peptide based on the sequence, WIFPWIQL, was selectively prone to recognize and bind to GC MKN45 cells in vitro, and also improve the delivery efficiency of polymeric micelles-encapsulated drugs into tumor cells and displayed better therapeutic outcome in experimental animals. This strategy of GRP78-mediated drug targeting system may bring chemotherapeutic drugs with more precise targeting to tumor cells, leading to minimize side effects on patients after chemotherapy.

Original languageEnglish
Pages (from-to)2584-2597
Number of pages14
JournalProteomics
Volume12
Issue number15-16
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Two-Dimensional Difference Gel Electrophoresis
Micelles
Stomach Neoplasms
Tumors
Cells
Biomarkers
Pharmaceutical Preparations
Tissue
alpha 1-Antitrypsin
Oncology
Chemotherapy
Therapeutics
Tumor Biomarkers
Transferases
Heterografts
Neoplasms
Glutathione
Animals
Peptides
Drug Delivery Systems

Keywords

  • 2D DIGE
  • Biomarker
  • Biomedicine
  • Gastric cancer
  • Glucose-regulated protein 78
  • Micelles

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Targeting to overexpressed glucose-regulated protein 78 in gastric cancer discovered by 2D DIGE improves the diagnostic and therapeutic efficacy of micelles-mediated system. / Cheng, Chun Chia; Lu, Norman; Peng, Cheng Liang; Chang, Chun Chao; Mai, Fu Der; Chen, Ling Yun; Liao, Mei Hsiu; Wang, Wen Ming; Chang, Jungshan.

In: Proteomics, Vol. 12, No. 15-16, 08.2012, p. 2584-2597.

Research output: Contribution to journalArticle

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abstract = "The survivals of gastric cancer (GC) patients are associated with early diagnosis and effective treatments. Therefore, it is urgent for the discovery of early GC biomarkers and tumor-targeting therapeutics. The aim of this study was to uncover putative tissue biomarkers of GC using 2D DIGE and then apply one of these specific markers in GC treatment. We found three putative biomarkers of GC with significant differences in expression level compared to adjacent normal tissue, including glucose-regulated protein 78 (GRP78) and glutathione s-transferase pi (GSTpi) with increased expression level, and alpha-1 antitrypsin (A1AT) with reduced expression level. The overexpressed GRP78 was used as a targeted protein for guiding the drugs to tumor cells, leading to more effective treatment for GC xenografts. Our results demonstrated that the designated GRP78-binding peptide based on the sequence, WIFPWIQL, was selectively prone to recognize and bind to GC MKN45 cells in vitro, and also improve the delivery efficiency of polymeric micelles-encapsulated drugs into tumor cells and displayed better therapeutic outcome in experimental animals. This strategy of GRP78-mediated drug targeting system may bring chemotherapeutic drugs with more precise targeting to tumor cells, leading to minimize side effects on patients after chemotherapy.",
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