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Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice

Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed...

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Autores principales: Zhang, Jia, Wang, Weiyi, Zhou, Yuan, Yang, Jing, Xu, Jingli, Xu, Zhiyuan, Xu, Beihua, Yan, Li, Cheng, Xiang-Dong, Li, Minghua, Qin, Jiang-Jiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157903/
https://www.ncbi.nlm.nih.gov/pubmed/32322210
http://dx.doi.org/10.3389/fphar.2020.00457
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author Zhang, Jia
Wang, Weiyi
Zhou, Yuan
Yang, Jing
Xu, Jingli
Xu, Zhiyuan
Xu, Beihua
Yan, Li
Cheng, Xiang-Dong
Li, Minghua
Qin, Jiang-Jiang
author_facet Zhang, Jia
Wang, Weiyi
Zhou, Yuan
Yang, Jing
Xu, Jingli
Xu, Zhiyuan
Xu, Beihua
Yan, Li
Cheng, Xiang-Dong
Li, Minghua
Qin, Jiang-Jiang
author_sort Zhang, Jia
collection PubMed
description Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and effective anti-PC therapeutic agents. We have recently identified a novel marine-derived natural product terphenyllin with potent anti-PC activity. The present study was designed to investigate the efficacy and mechanisms of action of terphenyllin in several human PC cell lines and an orthotopic PC mouse model. The results showed that terphenyllin significantly inhibited the viability of all PC cell lines with minimal effects on a normal human pancreatic cell line (HPNE). We next demonstrated the effects of terphenyllin on colony formation, apoptosis, migration, and invasion in both Panc1 and HPAC cell lines in a concentration-dependent manner. Terphenyllin also suppressed the tumor growth and metastasis in the Panc1 orthotopic mouse model. We further showed the profound effects of terphenyllin on the expression of apoptosis-associated proteins, including Bax, Bad, Puma, Bim(L), Bcl-2, phos-Bcl-2 (Ser70), Bcl-xL, caspase 7, and PARP, which contributed to its anti-PC activity. In summary, terphenyllin suppressed the PC cell growth and metastasis in vitro and in vivo and may be developed as an anti-PC therapeutic agent in the future.
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spelling pubmed-71579032020-04-22 Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice Zhang, Jia Wang, Weiyi Zhou, Yuan Yang, Jing Xu, Jingli Xu, Zhiyuan Xu, Beihua Yan, Li Cheng, Xiang-Dong Li, Minghua Qin, Jiang-Jiang Front Pharmacol Pharmacology Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and effective anti-PC therapeutic agents. We have recently identified a novel marine-derived natural product terphenyllin with potent anti-PC activity. The present study was designed to investigate the efficacy and mechanisms of action of terphenyllin in several human PC cell lines and an orthotopic PC mouse model. The results showed that terphenyllin significantly inhibited the viability of all PC cell lines with minimal effects on a normal human pancreatic cell line (HPNE). We next demonstrated the effects of terphenyllin on colony formation, apoptosis, migration, and invasion in both Panc1 and HPAC cell lines in a concentration-dependent manner. Terphenyllin also suppressed the tumor growth and metastasis in the Panc1 orthotopic mouse model. We further showed the profound effects of terphenyllin on the expression of apoptosis-associated proteins, including Bax, Bad, Puma, Bim(L), Bcl-2, phos-Bcl-2 (Ser70), Bcl-xL, caspase 7, and PARP, which contributed to its anti-PC activity. In summary, terphenyllin suppressed the PC cell growth and metastasis in vitro and in vivo and may be developed as an anti-PC therapeutic agent in the future. Frontiers Media S.A. 2020-04-08 /pmc/articles/PMC7157903/ /pubmed/32322210 http://dx.doi.org/10.3389/fphar.2020.00457 Text en Copyright © 2020 Zhang, Wang, Zhou, Yang, Xu, Xu, Xu, Yan, Cheng, Li and Qin 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
Zhang, Jia
Wang, Weiyi
Zhou, Yuan
Yang, Jing
Xu, Jingli
Xu, Zhiyuan
Xu, Beihua
Yan, Li
Cheng, Xiang-Dong
Li, Minghua
Qin, Jiang-Jiang
Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
title Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
title_full Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
title_fullStr Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
title_full_unstemmed Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
title_short Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
title_sort terphenyllin suppresses orthotopic pancreatic tumor growth and prevents metastasis in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157903/
https://www.ncbi.nlm.nih.gov/pubmed/32322210
http://dx.doi.org/10.3389/fphar.2020.00457
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