Targeting to overexpressed glucose-regulated protein 78 in gastric cancer discovered by 2D DIGE improves the diagnostic and therapeutic efficacy of micelles-mediated system.
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.
Graduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chun-Chia
CC
Cheng
Norman
N
Lu
Cheng-Liang
CL
Peng
Chun-Chao
CC
Chang
Fu-Der
FD
Mai
Ling-Yun
LY
Chen
Mei-Hsiu
MH
Liao
Wen-Ming
WM
Wang
Jungshan
J
Chang
D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D008823:Micelles; D008969:Molecular Sequence Data; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008024:Ligands; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin