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Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer-related death with the characteristics of chemoresistance and early metastasis. Panaxadiol, a triterpenoid saponin extracted from the roots of American ginseng, has been proved to display anti-tumor activity in colon cancer. In this study, we f...

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Autores principales: Fan, Xuhui, Fu, Haotian, Xie, Ni, Guo, Hangcheng, Fu, Tiantian, Shan, Yunfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544303/
https://www.ncbi.nlm.nih.gov/pubmed/34623971
http://dx.doi.org/10.18632/aging.203575
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author Fan, Xuhui
Fu, Haotian
Xie, Ni
Guo, Hangcheng
Fu, Tiantian
Shan, Yunfeng
author_facet Fan, Xuhui
Fu, Haotian
Xie, Ni
Guo, Hangcheng
Fu, Tiantian
Shan, Yunfeng
author_sort Fan, Xuhui
collection PubMed
description Pancreatic cancer is the fourth leading cause of cancer-related death with the characteristics of chemoresistance and early metastasis. Panaxadiol, a triterpenoid saponin extracted from the roots of American ginseng, has been proved to display anti-tumor activity in colon cancer. In this study, we found panaxadiol significantly inhibited proliferation, and induced apoptosis in human pancreatic cancer cell lines PANC-1 and Patu8988 in a dose-dependent manner. Furthermore, the expression of apoptosis-related proteins (Bax, Bcl2, Cleaved-caspase3) was detected via western blot and immunofluorescence staining. In addition, panaxadiol was also found to inhibit the migration of pancreatic cancer cells by wound healing and transwell assays. In vivo, the growth of xenograft pancreatic cancer models was also notably suppressed by panaxadiol compared to the control group. Moreover, the down-regulation of JAK2-STAT3 signaling pathway was responsible for the underlying pro-apoptosis mechanism of panaxadiol, and this result was in good agreement with molecular docking analysis between panaxadiol and STAT3. In conclusion, our work comprehensively explored the anti-tumor ability in PANC-1 and Patu8988 cells of panaxadiol and provided a potential choice for the clinical treatment of pancreatic cancer patients.
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spelling pubmed-85443032021-10-26 Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer Fan, Xuhui Fu, Haotian Xie, Ni Guo, Hangcheng Fu, Tiantian Shan, Yunfeng Aging (Albany NY) Research Paper Pancreatic cancer is the fourth leading cause of cancer-related death with the characteristics of chemoresistance and early metastasis. Panaxadiol, a triterpenoid saponin extracted from the roots of American ginseng, has been proved to display anti-tumor activity in colon cancer. In this study, we found panaxadiol significantly inhibited proliferation, and induced apoptosis in human pancreatic cancer cell lines PANC-1 and Patu8988 in a dose-dependent manner. Furthermore, the expression of apoptosis-related proteins (Bax, Bcl2, Cleaved-caspase3) was detected via western blot and immunofluorescence staining. In addition, panaxadiol was also found to inhibit the migration of pancreatic cancer cells by wound healing and transwell assays. In vivo, the growth of xenograft pancreatic cancer models was also notably suppressed by panaxadiol compared to the control group. Moreover, the down-regulation of JAK2-STAT3 signaling pathway was responsible for the underlying pro-apoptosis mechanism of panaxadiol, and this result was in good agreement with molecular docking analysis between panaxadiol and STAT3. In conclusion, our work comprehensively explored the anti-tumor ability in PANC-1 and Patu8988 cells of panaxadiol and provided a potential choice for the clinical treatment of pancreatic cancer patients. Impact Journals 2021-10-08 /pmc/articles/PMC8544303/ /pubmed/34623971 http://dx.doi.org/10.18632/aging.203575 Text en Copyright: © 2021 Fan et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Fan, Xuhui
Fu, Haotian
Xie, Ni
Guo, Hangcheng
Fu, Tiantian
Shan, Yunfeng
Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
title Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
title_full Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
title_fullStr Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
title_full_unstemmed Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
title_short Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
title_sort inhibition of jak2/stat3 signaling pathway by panaxadiol limits the progression of pancreatic cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544303/
https://www.ncbi.nlm.nih.gov/pubmed/34623971
http://dx.doi.org/10.18632/aging.203575
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