Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles

Sci Rep. 2016 Feb 11:6:20896. doi: 10.1038/srep20896.

Abstract

Hepatic metastasis is the leading cause of mortality of colon cancer, which is still lack of an effective therapy. A new delivery system, pluronic P85 block copolymers, conveying chemotherapeutic agent 5-fluorouracil (5-Fu) for inhibiting growth and metastasis of colon cancer was designed and developed. In this study, we demonstrated that 5-Fu produce strong pesticide effect at lower doses in the present of pluronic P85 compared with control groups. The migration and invasion of HCT116 cells and RKO cells were examined and the results showed that migration and invasion capacities of HCT116 cells and RKO cells were reduced by administering 5-Fu/P85 copolymer micelles in vitro and in vivo which indicating an effectively activity. Interestingly, the content of CD133 + CXCR4+ cells in HCT116 cancer cells and RKO cells treated by 5-Fu/P85 copolymer micelles was decreased. Importantly, the epithelial-mesenchymal transition (EMT) of CD133 + CXCR4+ cells, which was strongly associated with liver metastasis of colon cancer, was also suppressed by giving 5-Fu/P85 copolymer micelles. The results indicated that 5-Fu/P85 copolymer micelles could inhibit the growth and metastasis of colon cancer, which could be attributed to the decrease of the content of CD133 + CXCR4+ cells and suppression of EMT of CD133 + CXCR4+ cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen / genetics
  • AC133 Antigen / metabolism
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Fluorouracil / chemistry
  • Fluorouracil / pharmacology*
  • Gene Expression
  • HCT116 Cells
  • Humans
  • Injections, Intravenous
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Male
  • Mice
  • Mice, Nude
  • Micelles
  • Neoplasm Invasiveness
  • Poloxalene / chemistry*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Splenic Vein
  • Survival Analysis
  • Xenograft Model Antitumor Assays

Substances

  • AC133 Antigen
  • Antineoplastic Agents
  • Drug Carriers
  • Micelles
  • Receptors, CXCR4
  • pluronic block copolymer p85
  • Poloxalene
  • Fluorouracil