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

doi:10.1016/j.radonc.2016.02.007

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 journal › Article › peer-review

19 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 language	English
Pages (from-to)	282-90
Number of pages	9
Journal	Radiotherapy and Oncology
Volume	119
Issue number	2
DOIs	https://doi.org/10.1016/j.radonc.2016.02.007
Publication status	Published - May 2016
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.radonc.2016.02.007

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Shen, Y. A., Lan, K. L., Chang, C. H., Lin, L. T., He, C. L., Chen, P. H., Lee, T. W., Lee, Y. J., & Chuang, C. M. (2016). Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice. Radiotherapy and Oncology, 119(2), 282-90. https://doi.org/10.1016/j.radonc.2016.02.007

Shen, YA, Lan, KL, Chang, CH, Lin, LT, He, CL, Chen, PH, Lee, TW, Lee, YJ & Chuang, CM 2016, 'Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice', Radiotherapy and Oncology, vol. 119, no. 2, pp. 282-90. https://doi.org/10.1016/j.radonc.2016.02.007

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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.",

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",

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

year = "2016",

month = may,

doi = "10.1016/j.radonc.2016.02.007",

language = "English",

volume = "119",

pages = "282--90",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

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

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

SN - 0167-8140

VL - 119

SP - 282

EP - 290

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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