Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer

Yi-Qing Chen,* Wen-Ting Zhu,* Cai-Yan Lin, Zhong-Wen Yuan, Zhen-Hua Li, Peng-Ke Yan The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Ke YanThe Third Affiliated Hosp...

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Autores principales:	Chen YQ, Zhu WT, Lin CY, Yuan ZW, Li ZH, Yan PK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	rapamycin liposomes 5-fluorouracil akt/mtor p53 colorectal cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2341dbc096264beeade2337b03b04ecc
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spelling	oai:doaj.org-article:2341dbc096264beeade2337b03b04ecc2021-12-02T13:57:47ZDelivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer1178-2013https://doaj.org/article/2341dbc096264beeade2337b03b04ecc2021-01-01T00:00:00Zhttps://www.dovepress.com/delivery-of-rapamycin-by-liposomes-synergistically-enhances-the-chemot-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yi-Qing Chen,* Wen-Ting Zhu,* Cai-Yan Lin, Zhong-Wen Yuan, Zhen-Hua Li, Peng-Ke Yan The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Ke YanThe Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of ChinaEmail gysyypk@126.comBackground: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer.Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo.Results: The prepared rapamycin liposomes had a particle size of 100± 5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways.Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin’s antitumor effect but also synergistically enhances 5-FU’s chemotherapy effect.Keywords: rapamycin liposomes, 5-fluorouracil, Akt/mTOR, P53, colorectal cancerChen YQZhu WTLin CYYuan ZWLi ZHYan PKDove Medical Pressarticlerapamycin liposomes5-fluorouracilakt/mtorp53colorectal cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 269-281 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	rapamycin liposomes 5-fluorouracil akt/mtor p53 colorectal cancer Medicine (General) R5-920
spellingShingle	rapamycin liposomes 5-fluorouracil akt/mtor p53 colorectal cancer Medicine (General) R5-920 Chen YQ Zhu WT Lin CY Yuan ZW Li ZH Yan PK Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
description	Yi-Qing Chen,* Wen-Ting Zhu,* Cai-Yan Lin, Zhong-Wen Yuan, Zhen-Hua Li, Peng-Ke Yan The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Ke YanThe Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of ChinaEmail gysyypk@126.comBackground: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer.Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo.Results: The prepared rapamycin liposomes had a particle size of 100± 5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways.Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin’s antitumor effect but also synergistically enhances 5-FU’s chemotherapy effect.Keywords: rapamycin liposomes, 5-fluorouracil, Akt/mTOR, P53, colorectal cancer
format	article
author	Chen YQ Zhu WT Lin CY Yuan ZW Li ZH Yan PK
author_facet	Chen YQ Zhu WT Lin CY Yuan ZW Li ZH Yan PK
author_sort	Chen YQ
title	Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
title_short	Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
title_full	Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
title_fullStr	Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
title_full_unstemmed	Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
title_sort	delivery of rapamycin by liposomes synergistically enhances the chemotherapy effect of 5-fluorouracil on colorectal cancer
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/2341dbc096264beeade2337b03b04ecc
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Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer

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