Intraperitoneal188Re-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

Intraperitoneal¹⁸⁸Re-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: Journal article publication › Journal article › Academic research › peer-review

21 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 agent188Re-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 comparing188Re-BMEDA, a free form of188Re, with188Re-Liposome, a nanoparticle-encapsulated form of188Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. Results Intraperitoneal delivery of188Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of188Re-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)	282-290
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 - 1 May 2016
Externally published	Yes

Keywords

188 Re
Cancer stem cell
Liposome
Metabolic reprogramming
p53

ASJC Scopus subject areas

Hematology
Oncology
Radiology Nuclear Medicine and imaging

UN SDGs

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

More information

10.1016/j.radonc.2016.02.007

Cite this

Shen, Y. A., Lan, K. L., Chang, C. H., Lin, L., He, C. L., Chen, P. H., Lee, T. W., Lee, Y. J., & Chuang, C. M. (2016). Intraperitoneal¹⁸⁸Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice. Radiotherapy and Oncology, 119(2), 282-290. https://doi.org/10.1016/j.radonc.2016.02.007

@article{99ad847231c7432ca2227f212ed9d625,

title = "Intraperitoneal188Re-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 agent188Re-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 comparing188Re-BMEDA, a free form of188Re, with188Re-Liposome, a nanoparticle-encapsulated form of188Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. Results Intraperitoneal delivery of188Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of188Re-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",

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

year = "2016",

month = may,

day = "1",

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

language = "English",

volume = "119",

pages = "282--290",

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Shen, YA, Lan, KL, Chang, CH, Lin, L, He, CL, Chen, PH, Lee, TW, Lee, YJ & Chuang, CM 2016, 'Intraperitoneal¹⁸⁸Re-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. 282-290. https://doi.org/10.1016/j.radonc.2016.02.007

Intraperitoneal¹⁸⁸Re-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 et al.
In: Radiotherapy and Oncology, Vol. 119, No. 2, 01.05.2016, p. 282-290.

Research output: Journal article publication › Journal article › Academic research › peer-review

TY - JOUR

T1 - Intraperitoneal188Re-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 - 2016/5/1

Y1 - 2016/5/1

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 agent188Re-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 comparing188Re-BMEDA, a free form of188Re, with188Re-Liposome, a nanoparticle-encapsulated form of188Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. Results Intraperitoneal delivery of188Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of188Re-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 agent188Re-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 comparing188Re-BMEDA, a free form of188Re, with188Re-Liposome, a nanoparticle-encapsulated form of188Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. Results Intraperitoneal delivery of188Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of188Re-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 - 188 Re

KW - Cancer stem cell

KW - Liposome

KW - Metabolic reprogramming

KW - p53

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DO - 10.1016/j.radonc.2016.02.007

M3 - Journal article

C2 - 26915312

SN - 0167-8140

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SP - 282

EP - 290

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

IS - 2

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