Cargando…
β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling
β-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatmen...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331459/ https://www.ncbi.nlm.nih.gov/pubmed/30670971 http://dx.doi.org/10.3389/fphar.2018.01525 |
_version_ | 1783387135500353536 |
---|---|
author | Cao, Zhang-qi Wang, Xue-xi Lu, Li Xu, Jing-wen Li, Xiao-bin Zhang, Guang-ru Ma, Zhan-jun Shi, An-chen Wang, Yan Song, Yu-jun |
author_facet | Cao, Zhang-qi Wang, Xue-xi Lu, Li Xu, Jing-wen Li, Xiao-bin Zhang, Guang-ru Ma, Zhan-jun Shi, An-chen Wang, Yan Song, Yu-jun |
author_sort | Cao, Zhang-qi |
collection | PubMed |
description | β-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial–mesenchymal transition (EMT) markers and AKT/GSK-3β signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM. |
format | Online Article Text |
id | pubmed-6331459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63314592019-01-22 β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling Cao, Zhang-qi Wang, Xue-xi Lu, Li Xu, Jing-wen Li, Xiao-bin Zhang, Guang-ru Ma, Zhan-jun Shi, An-chen Wang, Yan Song, Yu-jun Front Pharmacol Pharmacology β-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial–mesenchymal transition (EMT) markers and AKT/GSK-3β signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM. Frontiers Media S.A. 2019-01-08 /pmc/articles/PMC6331459/ /pubmed/30670971 http://dx.doi.org/10.3389/fphar.2018.01525 Text en Copyright © 2019 Cao, Wang, Lu, Xu, Li, Zhang, Ma, Shi, Wang and Song. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Cao, Zhang-qi Wang, Xue-xi Lu, Li Xu, Jing-wen Li, Xiao-bin Zhang, Guang-ru Ma, Zhan-jun Shi, An-chen Wang, Yan Song, Yu-jun β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling |
title | β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling |
title_full | β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling |
title_fullStr | β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling |
title_full_unstemmed | β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling |
title_short | β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling |
title_sort | β-sitosterol and gemcitabine exhibit synergistic anti-pancreatic cancer activity by modulating apoptosis and inhibiting epithelial–mesenchymal transition by deactivating akt/gsk-3β signaling |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331459/ https://www.ncbi.nlm.nih.gov/pubmed/30670971 http://dx.doi.org/10.3389/fphar.2018.01525 |
work_keys_str_mv | AT caozhangqi bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT wangxuexi bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT luli bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT xujingwen bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT lixiaobin bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT zhangguangru bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT mazhanjun bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT shianchen bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT wangyan bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling AT songyujun bsitosterolandgemcitabineexhibitsynergisticantipancreaticcanceractivitybymodulatingapoptosisandinhibitingepithelialmesenchymaltransitionbydeactivatingaktgsk3bsignaling |