title: Anti-tumor efficacy of a therapeutic peptide based on thermo-responsive elastin-like polypeptide in combination with gemcitabine.
abstract: This work describes the effects of elastin-like polypeptide (ELP) with the p21(Waf1/Cip1)-derived cell cycle inhibitory peptide (p21) on pancreatic tumor cells with gemcitabine. The thermo-responsive property of ELP permits use of a mild, local hyperthermia to target tumors for the transport of chemotherapeutics. In this study, a p21-ELP construct with Bac cell penetrating peptide was designed, and its anticancer activities in pancreatic cancer cell lines was examined. In combination with gemcitabine, the peptide demonstrated enhanced in vitro cytotoxicity as well as tumor growth inhibition in an animal model. Our data suggest that this ELP construct, with gemcitabine, may improve pancreatic cancer therapy.
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States.
authors.forename: Jung Su
authors.initials: JS
authors.lastname: Ryu
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States. Electronic address: draucher@umc.edu.
authors.forename: Drazen
authors.initials: D
authors.lastname: Raucher
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000378:metabolism / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000378:metabolism / Q000494:pharmacology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D057846:Cell-Penetrating Peptides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D003841:Deoxycytidine; D004549:Elastin; D000093542:Gemcitabine
keywords: Anticancer drug delivery; Elastin-like polypeptide; Hyperthermia; Thermally targeting; p21