Anti-tumor efficacy of a therapeutic peptide based on thermo-responsive elastin-like polypeptide in combination with gemcitabine

Jung Su Ryu; Drazen Raucher

doi:10.1016/j.canlet.2014.03.021

Anti-tumor efficacy of a therapeutic peptide based on thermo-responsive elastin-like polypeptide in combination with gemcitabine

Cancer Lett. 2014 Jun 28;348(1-2):177-84. doi: 10.1016/j.canlet.2014.03.021. Epub 2014 Mar 26.

Authors

Jung Su Ryu¹, Drazen Raucher²

Affiliations

¹ Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States.
² Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States. Electronic address: draucher@umc.edu.

PMID: 24680816
DOI: 10.1016/j.canlet.2014.03.021

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.

Keywords: Anticancer drug delivery; Elastin-like polypeptide; Hyperthermia; Thermally targeting; p21.

MeSH terms

Active Transport, Cell Nucleus
Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell-Penetrating Peptides / metabolism
Cell-Penetrating Peptides / pharmacology
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / pharmacology
Deoxycytidine / analogs & derivatives
Deoxycytidine / pharmacology
Dose-Response Relationship, Drug
Elastin / metabolism
Elastin / pharmacology
Feasibility Studies
Female
Gemcitabine
Humans
Hypothermia, Induced*
Mice
Mice, Nude
Pancreatic Neoplasms / drug therapy*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology
Phosphorylation
Recombinant Fusion Proteins / metabolism
Recombinant Fusion Proteins / pharmacology
Retinoblastoma Protein / metabolism
S Phase Cell Cycle Checkpoints / drug effects
Time Factors
Xenograft Model Antitumor Assays

Substances

Cell-Penetrating Peptides
Cyclin-Dependent Kinase Inhibitor p21
Recombinant Fusion Proteins
Retinoblastoma Protein
Deoxycytidine
Elastin
Gemcitabine