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Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2
SIMPLE SUMMARY: The MAP kinase cascades are the most important oncogenic drivers of human cancers, including gastric cancer, and blocking this pathway with targeted inhibitors is an important antitumor strategy. Tegaserod maleate binds to MEK1 and MEK2, inhibiting kinase activity and thus suppressin...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332868/ https://www.ncbi.nlm.nih.gov/pubmed/35892850 http://dx.doi.org/10.3390/cancers14153592 |
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author | Wang, Zitong Chen, Yingying Li, Xiaoyu Zhang, Yuhan Zhao, Xiaokun Zhou, Hao Lu, Xuebo Zhao, Lili Yuan, Qiang Shi, Yunshu Zhao, Jimin Dong, Ziming Jiang, Yanan Liu, Kangdong |
author_facet | Wang, Zitong Chen, Yingying Li, Xiaoyu Zhang, Yuhan Zhao, Xiaokun Zhou, Hao Lu, Xuebo Zhao, Lili Yuan, Qiang Shi, Yunshu Zhao, Jimin Dong, Ziming Jiang, Yanan Liu, Kangdong |
author_sort | Wang, Zitong |
collection | PubMed |
description | SIMPLE SUMMARY: The MAP kinase cascades are the most important oncogenic drivers of human cancers, including gastric cancer, and blocking this pathway with targeted inhibitors is an important antitumor strategy. Tegaserod maleate binds to MEK1 and MEK2, inhibiting kinase activity and thus suppressing the MEK1/2-ERK1/2 signaling pathway. Thus, tegaserod maleate may have potential as a MEK1/2 inhibitor for gastric cancer. ABSTRACT: Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2. |
format | Online Article Text |
id | pubmed-9332868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93328682022-07-29 Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 Wang, Zitong Chen, Yingying Li, Xiaoyu Zhang, Yuhan Zhao, Xiaokun Zhou, Hao Lu, Xuebo Zhao, Lili Yuan, Qiang Shi, Yunshu Zhao, Jimin Dong, Ziming Jiang, Yanan Liu, Kangdong Cancers (Basel) Article SIMPLE SUMMARY: The MAP kinase cascades are the most important oncogenic drivers of human cancers, including gastric cancer, and blocking this pathway with targeted inhibitors is an important antitumor strategy. Tegaserod maleate binds to MEK1 and MEK2, inhibiting kinase activity and thus suppressing the MEK1/2-ERK1/2 signaling pathway. Thus, tegaserod maleate may have potential as a MEK1/2 inhibitor for gastric cancer. ABSTRACT: Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2. MDPI 2022-07-23 /pmc/articles/PMC9332868/ /pubmed/35892850 http://dx.doi.org/10.3390/cancers14153592 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Zitong Chen, Yingying Li, Xiaoyu Zhang, Yuhan Zhao, Xiaokun Zhou, Hao Lu, Xuebo Zhao, Lili Yuan, Qiang Shi, Yunshu Zhao, Jimin Dong, Ziming Jiang, Yanan Liu, Kangdong Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 |
title | Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 |
title_full | Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 |
title_fullStr | Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 |
title_full_unstemmed | Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 |
title_short | Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2 |
title_sort | tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting mek1/2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332868/ https://www.ncbi.nlm.nih.gov/pubmed/35892850 http://dx.doi.org/10.3390/cancers14153592 |
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