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SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells

Nowadays, nanoparticle-based drug delivery systems are recognized to reduce the therapeutic side effects. One of the common problems in cancer treatment is cancer drug resistance, resulting from the over-expression of one energy-dependent transporter that enhances drug efflux. Irinotecan is used for...

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Autores principales: Nagheh, Zahra, Irani, Shiva, Mirfakhraie, Reza, Dinarvand, Rassoul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700907/
https://www.ncbi.nlm.nih.gov/pubmed/28948511
http://dx.doi.org/10.1007/s40204-017-0073-y
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author Nagheh, Zahra
Irani, Shiva
Mirfakhraie, Reza
Dinarvand, Rassoul
author_facet Nagheh, Zahra
Irani, Shiva
Mirfakhraie, Reza
Dinarvand, Rassoul
author_sort Nagheh, Zahra
collection PubMed
description Nowadays, nanoparticle-based drug delivery systems are recognized to reduce the therapeutic side effects. One of the common problems in cancer treatment is cancer drug resistance, resulting from the over-expression of one energy-dependent transporter that enhances drug efflux. Irinotecan is used for metastatic colorectal cancer. The involvement of ABCG2 transporter in irinotecan resistance has been established. The current study was designed to characterize SN38-loaded pegylated (polyethylene glycol) PLGA [poly(lactic-co-glycolic acid)]-verapamil nanoparticles (NPs), and to distinguish the cytotoxic effect of SN38-PEG-PLGA-Ver NPs and the ability of SN38-PEG-PLGA-Ver NPs to inhibit drug resistance through the inhibition of ABCG2 expression. The surface morphology of nanoparticles was determined by scanning electron microscopy. The drug cytotoxicity of SN38-PEG-PLGA-verapamil nanoparticles was measured by MTT assay with desired concentrations and SN38-PEG-PLGA-Ver at different incubation times. Real-time PCR was used to determine the mRNA level of ABCG2, BAX, and BCL2. The cellular uptake assay was performed to show the cellular uptake of nanoparticles. The size of NPs used in this study was about 179 nm with surface charge of −17.1 mV. MTT assay results showed that 1 μmol/L of free drug and 3 μmol/L of NPs could reduce HT29 cells by half (IC(50)) after 48 and 96 h, respectively. An increase in expression of BAX and a decrease in expression of ABCG2 were observed according to the real-time PCR. No significant change was detected in expression of BCL2. In conclusion, sufficient uptake of SN38-PEG-PLGA-Ver NPs and a significant decrease in expression of ABCG2 and an increase in expression of BAX and BAX/BCL2 ratio was observed after treatment with nanoparticles compared with free SN38. These results reveal that SN38-PEG-PLGA-Ver NPs can be an effective therapeutic method in colon cancer treatments and also may prevent anticancer drug resistance.
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spelling pubmed-57009072017-12-04 SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells Nagheh, Zahra Irani, Shiva Mirfakhraie, Reza Dinarvand, Rassoul Prog Biomater Original Research Nowadays, nanoparticle-based drug delivery systems are recognized to reduce the therapeutic side effects. One of the common problems in cancer treatment is cancer drug resistance, resulting from the over-expression of one energy-dependent transporter that enhances drug efflux. Irinotecan is used for metastatic colorectal cancer. The involvement of ABCG2 transporter in irinotecan resistance has been established. The current study was designed to characterize SN38-loaded pegylated (polyethylene glycol) PLGA [poly(lactic-co-glycolic acid)]-verapamil nanoparticles (NPs), and to distinguish the cytotoxic effect of SN38-PEG-PLGA-Ver NPs and the ability of SN38-PEG-PLGA-Ver NPs to inhibit drug resistance through the inhibition of ABCG2 expression. The surface morphology of nanoparticles was determined by scanning electron microscopy. The drug cytotoxicity of SN38-PEG-PLGA-verapamil nanoparticles was measured by MTT assay with desired concentrations and SN38-PEG-PLGA-Ver at different incubation times. Real-time PCR was used to determine the mRNA level of ABCG2, BAX, and BCL2. The cellular uptake assay was performed to show the cellular uptake of nanoparticles. The size of NPs used in this study was about 179 nm with surface charge of −17.1 mV. MTT assay results showed that 1 μmol/L of free drug and 3 μmol/L of NPs could reduce HT29 cells by half (IC(50)) after 48 and 96 h, respectively. An increase in expression of BAX and a decrease in expression of ABCG2 were observed according to the real-time PCR. No significant change was detected in expression of BCL2. In conclusion, sufficient uptake of SN38-PEG-PLGA-Ver NPs and a significant decrease in expression of ABCG2 and an increase in expression of BAX and BAX/BCL2 ratio was observed after treatment with nanoparticles compared with free SN38. These results reveal that SN38-PEG-PLGA-Ver NPs can be an effective therapeutic method in colon cancer treatments and also may prevent anticancer drug resistance. Springer Berlin Heidelberg 2017-09-25 /pmc/articles/PMC5700907/ /pubmed/28948511 http://dx.doi.org/10.1007/s40204-017-0073-y Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Nagheh, Zahra
Irani, Shiva
Mirfakhraie, Reza
Dinarvand, Rassoul
SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells
title SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells
title_full SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells
title_fullStr SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells
title_full_unstemmed SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells
title_short SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells
title_sort sn38-peg-plga-verapamil nanoparticles inhibit proliferation and downregulate drug transporter abcg2 gene expression in colorectal cancer cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700907/
https://www.ncbi.nlm.nih.gov/pubmed/28948511
http://dx.doi.org/10.1007/s40204-017-0073-y
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