Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice

Yao An Shen, Keng Li Lan, Chih Hsien Chang, Liang Ting Lin, Chun Lin He, Po Hung Chen, Te Wei Lee, Yi Jang Lee, Chi Mu Chuang

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE: Cancer stem cells exhibit distinctive cellular metabolism compared with the more differentiated counterparts or normal cells. We aimed to investigate the impact of a novel radionuclide anti-cancer agent (188)Re-Liposome on stemness markers' expression and cellular metabolism in an ovarian cancer model.

MATERIAL AND METHODS: A 2×2 factorial experiment was designed in which factor 1 represented the drug treatment comparing (188)Re-BMEDA, a free form of (188)Re, with (188)Re-Liposome, a nanoparticle-encapsulated form of (188)Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery.

RESULTS: Intraperitoneal delivery of (188)Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of (188)Re-Liposome treatment was able to block epithelial-to-mesenchymal transition (EMT) and reactivate p53 function. Collectively, these molecular changes led to a striking tumour-killing effect.

CONCLUSIONS: Radionuclides encapsulated in liposomes may represent a novel treatment for ovarian cancer when delivered intraperitoneally (a type of loco-regional delivery). In the future, this concept may be further extended for the treatment of several relevant cancers that have been proved to be suitable for loco-regional delivery of therapeutic agents, such as colon cancer, gastric cancer, and pancreatic cancer.

Original languageEnglish
Pages (from-to)282-90
Number of pages9
JournalRadiotherapy and Oncology
Volume119
Issue number2
DOIs
Publication statusPublished - May 2016
Externally publishedYes

Keywords

  • Animals
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Glycolysis
  • Humans
  • Liposomes
  • Mice
  • Ovarian Neoplasms/metabolism
  • Oxidative Phosphorylation
  • Radiation Tolerance
  • Radioisotopes/administration & dosage
  • Rhenium/administration & dosage
  • Tumor Suppressor Protein p53/physiology

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