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Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer

Optimizing the currently available treatment options for pancreatic cancer (PC) is a priority. Cabazitaxel (CTX), a semisynthetic taxane, is mainly used for treating patients with PC who are resistant to paclitaxel (PTX) or docetaxel, due its poor affinity for P-glycoprotein. However, there are only...

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Autores principales: Li, Zequn, Xuan, Zefeng, Chen, Jian, Song, Wenfeng, Zhang, Shiyu, Jin, Cheng, Zhou, Mengqiao, Zheng, Shusen, Song, Penghong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252454/
https://www.ncbi.nlm.nih.gov/pubmed/32377719
http://dx.doi.org/10.3892/ijo.2020.5053
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author Li, Zequn
Xuan, Zefeng
Chen, Jian
Song, Wenfeng
Zhang, Shiyu
Jin, Cheng
Zhou, Mengqiao
Zheng, Shusen
Song, Penghong
author_facet Li, Zequn
Xuan, Zefeng
Chen, Jian
Song, Wenfeng
Zhang, Shiyu
Jin, Cheng
Zhou, Mengqiao
Zheng, Shusen
Song, Penghong
author_sort Li, Zequn
collection PubMed
description Optimizing the currently available treatment options for pancreatic cancer (PC) is a priority. Cabazitaxel (CTX), a semisynthetic taxane, is mainly used for treating patients with PC who are resistant to paclitaxel (PTX) or docetaxel, due its poor affinity for P-glycoprotein. However, there are only a few studies demonstrating the effect of CTX on PC. The present study aimed to investigate the efficiency and underlying mechanism of CTX in PC treatment. Cell proliferation, colony formation assay and apoptosis analysis were achieved in the two human PC cell lines AsPC-1 and BxPC-3. Drug sensitivity test was performed in BxPC-3 tumor-bearing mice. The results demonstrated that CTX had a lower half maximal inhibitory concentration compared with PTX for the inhibition of cell proliferation, both in vivo and in vitro. Furthermore, the nuclear factor-κB (NF-κB) pathway was activated following cell treatment with CTX, and NF-κB p65 overexpression attenuated CTX cytotoxicity. In addition, the combined use of the specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) with CTX significantly enhanced CTX effect, both in vivo and in vitro. Similarly, the mRNA and protein expression of B-cell lymphoma-2 was decreased in AsPC-1 and BxPC-3 cells following treatment with CTX and CAPE, suggesting that NF-κB may serve a crucial role in CTX efficiency. In conclusion, results from our previous study indicated that CTX could potentially replace PTX in the treatment of PC, and the present study demonstrated that CTX combination with an NF-κB inhibitor may be considered as a potential therapeutic option for PC, which may improve the prognosis of patients with PC.
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spelling pubmed-72524542020-05-28 Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer Li, Zequn Xuan, Zefeng Chen, Jian Song, Wenfeng Zhang, Shiyu Jin, Cheng Zhou, Mengqiao Zheng, Shusen Song, Penghong Int J Oncol Articles Optimizing the currently available treatment options for pancreatic cancer (PC) is a priority. Cabazitaxel (CTX), a semisynthetic taxane, is mainly used for treating patients with PC who are resistant to paclitaxel (PTX) or docetaxel, due its poor affinity for P-glycoprotein. However, there are only a few studies demonstrating the effect of CTX on PC. The present study aimed to investigate the efficiency and underlying mechanism of CTX in PC treatment. Cell proliferation, colony formation assay and apoptosis analysis were achieved in the two human PC cell lines AsPC-1 and BxPC-3. Drug sensitivity test was performed in BxPC-3 tumor-bearing mice. The results demonstrated that CTX had a lower half maximal inhibitory concentration compared with PTX for the inhibition of cell proliferation, both in vivo and in vitro. Furthermore, the nuclear factor-κB (NF-κB) pathway was activated following cell treatment with CTX, and NF-κB p65 overexpression attenuated CTX cytotoxicity. In addition, the combined use of the specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) with CTX significantly enhanced CTX effect, both in vivo and in vitro. Similarly, the mRNA and protein expression of B-cell lymphoma-2 was decreased in AsPC-1 and BxPC-3 cells following treatment with CTX and CAPE, suggesting that NF-κB may serve a crucial role in CTX efficiency. In conclusion, results from our previous study indicated that CTX could potentially replace PTX in the treatment of PC, and the present study demonstrated that CTX combination with an NF-κB inhibitor may be considered as a potential therapeutic option for PC, which may improve the prognosis of patients with PC. D.A. Spandidos 2020-04-27 /pmc/articles/PMC7252454/ /pubmed/32377719 http://dx.doi.org/10.3892/ijo.2020.5053 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Li, Zequn
Xuan, Zefeng
Chen, Jian
Song, Wenfeng
Zhang, Shiyu
Jin, Cheng
Zhou, Mengqiao
Zheng, Shusen
Song, Penghong
Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer
title Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer
title_full Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer
title_fullStr Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer
title_full_unstemmed Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer
title_short Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer
title_sort inhibiting the nf-κb pathway enhances the antitumor effect of cabazitaxel by downregulating bcl-2 in pancreatic cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252454/
https://www.ncbi.nlm.nih.gov/pubmed/32377719
http://dx.doi.org/10.3892/ijo.2020.5053
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