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Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway

While Bufalin restrains primary tumorigenesis, the role of Bufalin in cervical cancer remains unclear. Here, we show that Bufalin can inhibit cervical cancer cell proliferation, block cell cycle in G2/M phase, induce cellular apoptosis and reduce cell metastasis through stimulation of p21(waf/cip1),...

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Detalles Bibliográficos
Autores principales: Liu, Fei, Tong, Duo, Li, Haoran, Liu, Mingming, Li, Jiajia, Wang, Ziliang, Cheng, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891012/
https://www.ncbi.nlm.nih.gov/pubmed/26758421
http://dx.doi.org/10.18632/oncotarget.6840
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author Liu, Fei
Tong, Duo
Li, Haoran
Liu, Mingming
Li, Jiajia
Wang, Ziliang
Cheng, Xi
author_facet Liu, Fei
Tong, Duo
Li, Haoran
Liu, Mingming
Li, Jiajia
Wang, Ziliang
Cheng, Xi
author_sort Liu, Fei
collection PubMed
description While Bufalin restrains primary tumorigenesis, the role of Bufalin in cervical cancer remains unclear. Here, we show that Bufalin can inhibit cervical cancer cell proliferation, block cell cycle in G2/M phase, induce cellular apoptosis and reduce cell metastasis through stimulation of p21(waf/cip1), p27(cip/kip), Bax and E-cadherin, and suppression of cyclin A, cyclin B1, CDK2, Bcl-2, Bcl-xl, MMP9 and SNAIL1. Further study suggests that Bufalin has no apparent damage to human normal cervical cells at the low concentration (<20nM), but increases the chemotherapeutic efficacy of paclitaxel. Mechanistic study reveals that Bufalin suppresses the integrin α2/FAK/AKT1/ GSK3β signaling. Finally, in vivo studies show that Bufalin blocks the Siha-induced xenograft tumor growth without detectable toxicity in the animals at the therapeutic doses, and the combination treatment of Bufalin and paclitaxel more efficiently inhibits xenograft tumor growth. Thus, Bufalin may be developed as a potential therapeutic agent to treat cervical cancer.
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spelling pubmed-48910122016-06-20 Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway Liu, Fei Tong, Duo Li, Haoran Liu, Mingming Li, Jiajia Wang, Ziliang Cheng, Xi Oncotarget Research Paper While Bufalin restrains primary tumorigenesis, the role of Bufalin in cervical cancer remains unclear. Here, we show that Bufalin can inhibit cervical cancer cell proliferation, block cell cycle in G2/M phase, induce cellular apoptosis and reduce cell metastasis through stimulation of p21(waf/cip1), p27(cip/kip), Bax and E-cadherin, and suppression of cyclin A, cyclin B1, CDK2, Bcl-2, Bcl-xl, MMP9 and SNAIL1. Further study suggests that Bufalin has no apparent damage to human normal cervical cells at the low concentration (<20nM), but increases the chemotherapeutic efficacy of paclitaxel. Mechanistic study reveals that Bufalin suppresses the integrin α2/FAK/AKT1/ GSK3β signaling. Finally, in vivo studies show that Bufalin blocks the Siha-induced xenograft tumor growth without detectable toxicity in the animals at the therapeutic doses, and the combination treatment of Bufalin and paclitaxel more efficiently inhibits xenograft tumor growth. Thus, Bufalin may be developed as a potential therapeutic agent to treat cervical cancer. Impact Journals LLC 2016-01-07 /pmc/articles/PMC4891012/ /pubmed/26758421 http://dx.doi.org/10.18632/oncotarget.6840 Text en Copyright: © 2016 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Fei
Tong, Duo
Li, Haoran
Liu, Mingming
Li, Jiajia
Wang, Ziliang
Cheng, Xi
Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway
title Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway
title_full Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway
title_fullStr Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway
title_full_unstemmed Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway
title_short Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway
title_sort bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/fak signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891012/
https://www.ncbi.nlm.nih.gov/pubmed/26758421
http://dx.doi.org/10.18632/oncotarget.6840
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