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Radiother Oncol. 2016 May;119(2):282-90. doi: 10.1016/j.radonc.2016.02.007. Epub 2016 Feb 22.

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

Author information

1
Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
2
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Oncology, Taipei Veterans General Hospital, Taiwan.
3
Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan; Institute of Nuclear Energy Research, Taiwan.
4
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
5
Department of Obstetrics and Gynaecology, Taipei Veterans General Hospital, Taiwan.
6
Institute of Nuclear Energy Research, Taiwan.
7
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynaecology, Taipei Veterans General Hospital, Taiwan. Electronic address: cmjuang@gmail.com.

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.

KEYWORDS:

(188)Re; Cancer stem cell; Liposome; Metabolic reprogramming; p53

PMID:
26915312
DOI:
10.1016/j.radonc.2016.02.007
[Indexed for MEDLINE]
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