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 journalArticle

7 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

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Oxidative Phosphorylation
Glycolysis
Liposomes
Ovarian Neoplasms
Growth
Neoplasms
Radioisotopes
Stomach Neoplasms
Therapeutics
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Pancreatic Neoplasms
Nanoparticles
Colonic Neoplasms
Pharmaceutical Preparations

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

Cite this

Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice. / Shen, Yao An; Lan, Keng Li; Chang, Chih Hsien; Lin, Liang Ting; He, Chun Lin; Chen, Po Hung; Lee, Te Wei; Lee, Yi Jang; Chuang, Chi Mu.

In: Radiotherapy and Oncology, Vol. 119, No. 2, 05.2016, p. 282-90.

Research output: Contribution to journalArticle

Shen, Yao An ; Lan, Keng Li ; Chang, Chih Hsien ; Lin, Liang Ting ; He, Chun Lin ; Chen, Po Hung ; Lee, Te Wei ; Lee, Yi Jang ; Chuang, Chi Mu. / Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice. In: Radiotherapy and Oncology. 2016 ; Vol. 119, No. 2. pp. 282-90.
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title = "Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice",
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.",
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T1 - Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice

AU - Shen, Yao An

AU - Lan, Keng Li

AU - Chang, Chih Hsien

AU - Lin, Liang Ting

AU - He, Chun Lin

AU - Chen, Po Hung

AU - Lee, Te Wei

AU - Lee, Yi Jang

AU - Chuang, Chi Mu

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2016/5

Y1 - 2016/5

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line, Tumor

KW - Epithelial-Mesenchymal Transition

KW - Female

KW - Glycolysis

KW - Humans

KW - Liposomes

KW - Mice

KW - Ovarian Neoplasms/metabolism

KW - Oxidative Phosphorylation

KW - Radiation Tolerance

KW - Radioisotopes/administration & dosage

KW - Rhenium/administration & dosage

KW - Tumor Suppressor Protein p53/physiology

U2 - 10.1016/j.radonc.2016.02.007

DO - 10.1016/j.radonc.2016.02.007

M3 - Article

C2 - 26915312

VL - 119

SP - 282

EP - 290

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

SN - 0167-8140

IS - 2

ER -