A WKYMVm-Containing Combination Elicits Potent Anti-Tumor Activity in Heterotopic Cancer Animal Model

Title
A WKYMVm-Containing Combination Elicits Potent Anti-Tumor Activity in Heterotopic Cancer Animal Model
Author(s)
백석환김상두[김상두]이하영[이하영]심재웅[심재웅]김학정[김학정]Brian A. Zabel[Brian A. Zabel]배외식[배외식]
Keywords
FORMYL PEPTIDE RECEPTOR; VAL-D-MET; CD8(+) T-CELLS; DENDRITIC CELLS; PHOSPHOINOSITIDE HYDROLYSIS; SUPEROXIDE GENERATION; GROWTH-INHIBITION; IMMUNOTHERAPY; EXPRESSION; CHEMOATTRACTANT
Issue Date
201201
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.7, no.1
Abstract
The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm), 5-fluoro-uracil (5-FU), and mature dendritic cells (mDCs) against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK) cells into the tumor. The production of two cytokines, IFN-gamma and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti-tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment.
URI
http://hdl.handle.net/YU.REPOSITORY/29998http://dx.doi.org/10.1371/journal.pone.0030522
ISSN
1932-6203
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의과대학 > 생화학.분자생물학교실 > Articles
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