Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

The major challenges we are facing in cancer therapy with paclitaxel (PTX) are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel...

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Autores principales:	Zhen Hua Wu, Ming-ke Lu, Long Yu Hu, Xiaotong Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b14f78475d74842a0f671bc4c06ff69
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spelling	oai:doaj.org-article:3b14f78475d74842a0f671bc4c06ff692021-11-18T08:05:17ZPraziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.1932-620310.1371/journal.pone.0051721https://doaj.org/article/3b14f78475d74842a0f671bc4c06ff692012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251610/?tool=EBIhttps://doaj.org/toc/1932-6203The major challenges we are facing in cancer therapy with paclitaxel (PTX) are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ), an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.Zhen Hua WuMing-ke LuLong Yu HuXiaotong LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51721 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhen Hua Wu Ming-ke Lu Long Yu Hu Xiaotong Li Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
description	The major challenges we are facing in cancer therapy with paclitaxel (PTX) are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ), an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.
format	article
author	Zhen Hua Wu Ming-ke Lu Long Yu Hu Xiaotong Li
author_facet	Zhen Hua Wu Ming-ke Lu Long Yu Hu Xiaotong Li
author_sort	Zhen Hua Wu
title	Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
title_short	Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
title_full	Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
title_fullStr	Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
title_full_unstemmed	Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
title_sort	praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3b14f78475d74842a0f671bc4c06ff69
work_keys_str_mv	AT zhenhuawu praziquantelsynergisticallyenhancespaclitaxelefficacytoinhibitcancercellgrowth AT mingkelu praziquantelsynergisticallyenhancespaclitaxelefficacytoinhibitcancercellgrowth AT longyuhu praziquantelsynergisticallyenhancespaclitaxelefficacytoinhibitcancercellgrowth AT xiaotongli praziquantelsynergisticallyenhancespaclitaxelefficacytoinhibitcancercellgrowth
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Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

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