Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis

Hong Zou,1,2 Li Li,1 Ines Garcia Carcedo,1 Zhi Ping Xu,1 Michael Monteiro,1 Wenyi Gu1 1Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Brisbane, QLD, Australia; 2Department of Pathology, Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shi...

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Autores principales:	Zou H, Li L, Garcia Carcedo I, Xu ZP, Monteiro M, Gu WY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	BEZ235 PI3K/Akt/mTOR Paclitaxel Colon cancer Nanoemulsion Apoptosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/97c1c0907c4440d1bb6c861ea9ae6a5c
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spelling	oai:doaj.org-article:97c1c0907c4440d1bb6c861ea9ae6a5c2021-12-02T06:32:31ZSynergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis1178-2013https://doaj.org/article/97c1c0907c4440d1bb6c861ea9ae6a5c2016-05-01T00:00:00Zhttps://www.dovepress.com/synergistic-inhibition-of-colon-cancer-cell-growth-with-nanoemulsion-l-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hong Zou,1,2 Li Li,1 Ines Garcia Carcedo,1 Zhi Ping Xu,1 Michael Monteiro,1 Wenyi Gu1 1Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Brisbane, QLD, Australia; 2Department of Pathology, Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezhi University, Xinjiang, People’s Republic of China Abstract: Colon cancer is the third most common cancer in the world, with drug resistance and metastasis being the major challenges to effective treatments. To overcome this, combination therapy with different chemotherapeutics is a common practice. In this study, we demonstrated that paclitaxel (PTX) together with BEZ235 exhibited a synergetic inhibition effect on colon cancer cell growth. Furthermore, nanoemulsion (NE)-loaded PTX and BEZ235 were more effective than the free drug, and a combination treatment of both NE drugs increased the efficiency of the treatments. BEZ235 pretreatment before adding PTX sensitized the cancer cells further, suggesting a synergistic inhibition effect through the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin pathway. The 50% inhibitory concentrations for BEZ235 were 127.1 nM and 145.0 nM and for PTX 9.7 nM and 9.5 nM for HCT-116 and HT-29 cells, respectively. When loaded with NE the 50% inhibitory concentrations for BEZ235 decreased to 52.6 nM and 55.6 nM and for PTX to 1.9 nM and 2.3 nM for HCT-116 and HT-29 cells, respectively. Combination treatment with 10 nM NE-BEZ235 and 0.6 nM and 1.78 nM NE-PTX could kill 50% of HCT-116 and HT-29, respectively. The cell death caused by the treatment was through apoptotic cell death, which coincided with decreased expression of anti-apoptotic protein B-cell lymphoma 2. Our data indicate that the combination therapy of PTX with the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin dual inhibitor BEZ235 using NE delivery may hold promise for a more effective approach for colon cancer treatment. Keywords: combination therapy, signal pathway inhibitor, chemotherapy, nanomedicineZou HLi LGarcia Carcedo IXu ZPMonteiro MGu WYDove Medical PressarticleBEZ235PI3K/Akt/mTORPaclitaxelColon cancerNanoemulsionApoptosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1947-1958 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	BEZ235 PI3K/Akt/mTOR Paclitaxel Colon cancer Nanoemulsion Apoptosis Medicine (General) R5-920
spellingShingle	BEZ235 PI3K/Akt/mTOR Paclitaxel Colon cancer Nanoemulsion Apoptosis Medicine (General) R5-920 Zou H Li L Garcia Carcedo I Xu ZP Monteiro M Gu WY Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis
description	Hong Zou,1,2 Li Li,1 Ines Garcia Carcedo,1 Zhi Ping Xu,1 Michael Monteiro,1 Wenyi Gu1 1Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Brisbane, QLD, Australia; 2Department of Pathology, Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezhi University, Xinjiang, People’s Republic of China Abstract: Colon cancer is the third most common cancer in the world, with drug resistance and metastasis being the major challenges to effective treatments. To overcome this, combination therapy with different chemotherapeutics is a common practice. In this study, we demonstrated that paclitaxel (PTX) together with BEZ235 exhibited a synergetic inhibition effect on colon cancer cell growth. Furthermore, nanoemulsion (NE)-loaded PTX and BEZ235 were more effective than the free drug, and a combination treatment of both NE drugs increased the efficiency of the treatments. BEZ235 pretreatment before adding PTX sensitized the cancer cells further, suggesting a synergistic inhibition effect through the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin pathway. The 50% inhibitory concentrations for BEZ235 were 127.1 nM and 145.0 nM and for PTX 9.7 nM and 9.5 nM for HCT-116 and HT-29 cells, respectively. When loaded with NE the 50% inhibitory concentrations for BEZ235 decreased to 52.6 nM and 55.6 nM and for PTX to 1.9 nM and 2.3 nM for HCT-116 and HT-29 cells, respectively. Combination treatment with 10 nM NE-BEZ235 and 0.6 nM and 1.78 nM NE-PTX could kill 50% of HCT-116 and HT-29, respectively. The cell death caused by the treatment was through apoptotic cell death, which coincided with decreased expression of anti-apoptotic protein B-cell lymphoma 2. Our data indicate that the combination therapy of PTX with the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin dual inhibitor BEZ235 using NE delivery may hold promise for a more effective approach for colon cancer treatment. Keywords: combination therapy, signal pathway inhibitor, chemotherapy, nanomedicine
format	article
author	Zou H Li L Garcia Carcedo I Xu ZP Monteiro M Gu WY
author_facet	Zou H Li L Garcia Carcedo I Xu ZP Monteiro M Gu WY
author_sort	Zou H
title	Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis
title_short	Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis
title_full	Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis
title_fullStr	Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis
title_full_unstemmed	Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis
title_sort	synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and pi3k/mtor dual inhibitor bez235 through apoptosis
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/97c1c0907c4440d1bb6c861ea9ae6a5c
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Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis

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