Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells

Abstract Colorectal cancer is a major cancer type worldwide. 5-fluorouracil, often given with leucovorin, is the most commonly used drug in colorectal cancer chemotherapy, yet development of drug resistance to 5-fluorouracil in colorectal cancer cells is the primary cause of chemotherapy failure. Mo...

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Autores principales:	Shu Wang, Lei Wang, Zhiyang Zhou, Qipan Deng, Ling Li, Mingzhi Zhang, Linlin Liu, Yong Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e6684641dae4958a4e0e768366c3204
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spelling	oai:doaj.org-article:7e6684641dae4958a4e0e768366c32042021-12-02T16:08:10ZLeucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells10.1038/s41598-017-00839-92045-2322https://doaj.org/article/7e6684641dae4958a4e0e768366c32042017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00839-9https://doaj.org/toc/2045-2322Abstract Colorectal cancer is a major cancer type worldwide. 5-fluorouracil, often given with leucovorin, is the most commonly used drug in colorectal cancer chemotherapy, yet development of drug resistance to 5-fluorouracil in colorectal cancer cells is the primary cause of chemotherapy failure. Most patients receiving intravenous 5-fluorouracil develop side effects. Leucovorin, due to its vitamin-like profile, has few side-effects. Drug repurposing is the application of approved drugs to treat new indications. In this study, we performed a novel drug-repurposing screening to identify Food and Drug Administration-approved chemotherapeutic compounds possessing synergistic activity with leucovorin against colorectal cancer cells. We found that the combination of bortezomib and leucovorin enhanced caspase activation and increased apoptosis in colorectal cancer cells better than either agent alone. Further, the synergistic induction of apoptosis and inhibition of tumor growth were also observed in mouse colorectal cancer xenografts. These data support leucovorin enhances the anti-cancer effect of bortezomib and present this novel combinatorial treatment against colorectal cancer.Shu WangLei WangZhiyang ZhouQipan DengLing LiMingzhi ZhangLinlin LiuYong LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shu Wang Lei Wang Zhiyang Zhou Qipan Deng Ling Li Mingzhi Zhang Linlin Liu Yong Li Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells
description	Abstract Colorectal cancer is a major cancer type worldwide. 5-fluorouracil, often given with leucovorin, is the most commonly used drug in colorectal cancer chemotherapy, yet development of drug resistance to 5-fluorouracil in colorectal cancer cells is the primary cause of chemotherapy failure. Most patients receiving intravenous 5-fluorouracil develop side effects. Leucovorin, due to its vitamin-like profile, has few side-effects. Drug repurposing is the application of approved drugs to treat new indications. In this study, we performed a novel drug-repurposing screening to identify Food and Drug Administration-approved chemotherapeutic compounds possessing synergistic activity with leucovorin against colorectal cancer cells. We found that the combination of bortezomib and leucovorin enhanced caspase activation and increased apoptosis in colorectal cancer cells better than either agent alone. Further, the synergistic induction of apoptosis and inhibition of tumor growth were also observed in mouse colorectal cancer xenografts. These data support leucovorin enhances the anti-cancer effect of bortezomib and present this novel combinatorial treatment against colorectal cancer.
format	article
author	Shu Wang Lei Wang Zhiyang Zhou Qipan Deng Ling Li Mingzhi Zhang Linlin Liu Yong Li
author_facet	Shu Wang Lei Wang Zhiyang Zhou Qipan Deng Ling Li Mingzhi Zhang Linlin Liu Yong Li
author_sort	Shu Wang
title	Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells
title_short	Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells
title_full	Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells
title_fullStr	Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells
title_full_unstemmed	Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells
title_sort	leucovorin enhances the anti-cancer effect of bortezomib in colorectal cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7e6684641dae4958a4e0e768366c3204
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_version_	1718384606188666880

Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells

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