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Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway

Background: Oxaliplatin (OXA) resistance is a main obstacle to the chemotherapy of colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT), which is mainly regulated by TGF-β/Smad signaling pathway, has gradually been recognized as an important mechanism for tumor chemoresistance. Studies h...

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Autores principales: Yin, Jiahuan, Wang, Li, Wang, Yong, Shen, Hailong, Wang, Xiaojie, Wu, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529728/
https://www.ncbi.nlm.nih.gov/pubmed/31190888
http://dx.doi.org/10.2147/OTT.S199601
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author Yin, Jiahuan
Wang, Li
Wang, Yong
Shen, Hailong
Wang, Xiaojie
Wu, Lei
author_facet Yin, Jiahuan
Wang, Li
Wang, Yong
Shen, Hailong
Wang, Xiaojie
Wu, Lei
author_sort Yin, Jiahuan
collection PubMed
description Background: Oxaliplatin (OXA) resistance is a main obstacle to the chemotherapy of colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT), which is mainly regulated by TGF-β/Smad signaling pathway, has gradually been recognized as an important mechanism for tumor chemoresistance. Studies have shown that curcumin regulated EMT processes in many human cancers. However, whether curcumin could regulate OXA resistance in CRC through modulating TGF-β/Smad signaling-mediated EMT remains unclear. Methods: In an attempt to investigate the effect of curcumin on OXA resistance in CRC, OXA-resistant cell line HCT116/OXA was established firstly. The effect of curcumin on cell proliferation was evaluated by MTT assay and Ki67 immunofluorescence staining, respectively. Cell apoptosis was evaluated by flow cytometry. In addition, transwell assay was used to detect the effect of curcumin on cell invasion and the activation of TGF-β/Smad signaling was examined by immunofluorescence and Western blot. Moreover, the therapeutic potential of curcumin was further examined in vivo using a CRC animal model. Results: The OXA-resistant cell line HCT116/OXA was successfully established, and combination of OXA with curcumin reduced OXA resistance in vitro. Besides, the combination treatment inhibited the expressions of p-p65 and Bcl-2, but increased the level of active-caspase3. In addition, curcumin inhibited EMT via regulation of TGF-β/Smad2/3 signaling pathway. Moreover, in vivo study confirmed curcumin could reverse OXA resistance in CRC. Conclusion: Our study indicated that curcumin could reserve OXA resistance in CRC through dampening TGF-β/Smads signaling in vitro and in vivo.
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spelling pubmed-65297282019-06-12 Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway Yin, Jiahuan Wang, Li Wang, Yong Shen, Hailong Wang, Xiaojie Wu, Lei Onco Targets Ther Original Research Background: Oxaliplatin (OXA) resistance is a main obstacle to the chemotherapy of colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT), which is mainly regulated by TGF-β/Smad signaling pathway, has gradually been recognized as an important mechanism for tumor chemoresistance. Studies have shown that curcumin regulated EMT processes in many human cancers. However, whether curcumin could regulate OXA resistance in CRC through modulating TGF-β/Smad signaling-mediated EMT remains unclear. Methods: In an attempt to investigate the effect of curcumin on OXA resistance in CRC, OXA-resistant cell line HCT116/OXA was established firstly. The effect of curcumin on cell proliferation was evaluated by MTT assay and Ki67 immunofluorescence staining, respectively. Cell apoptosis was evaluated by flow cytometry. In addition, transwell assay was used to detect the effect of curcumin on cell invasion and the activation of TGF-β/Smad signaling was examined by immunofluorescence and Western blot. Moreover, the therapeutic potential of curcumin was further examined in vivo using a CRC animal model. Results: The OXA-resistant cell line HCT116/OXA was successfully established, and combination of OXA with curcumin reduced OXA resistance in vitro. Besides, the combination treatment inhibited the expressions of p-p65 and Bcl-2, but increased the level of active-caspase3. In addition, curcumin inhibited EMT via regulation of TGF-β/Smad2/3 signaling pathway. Moreover, in vivo study confirmed curcumin could reverse OXA resistance in CRC. Conclusion: Our study indicated that curcumin could reserve OXA resistance in CRC through dampening TGF-β/Smads signaling in vitro and in vivo. Dove 2019-05-17 /pmc/articles/PMC6529728/ /pubmed/31190888 http://dx.doi.org/10.2147/OTT.S199601 Text en © 2019 Yin et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Yin, Jiahuan
Wang, Li
Wang, Yong
Shen, Hailong
Wang, Xiaojie
Wu, Lei
Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway
title Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway
title_full Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway
title_fullStr Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway
title_full_unstemmed Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway
title_short Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway
title_sort curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of tgf-β/smad2/3 signaling pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529728/
https://www.ncbi.nlm.nih.gov/pubmed/31190888
http://dx.doi.org/10.2147/OTT.S199601
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