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Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway
Oxaliplatin-based therapy is used as a first-line drug to treat metastatic colorectal cancer. However, long-term and repeated drug treatment resulted in drug resistance and the failure of chemotherapy. Various natural compounds were previously reported to act as chemosensitizers to reverse drug resi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969589/ https://www.ncbi.nlm.nih.gov/pubmed/36860929 http://dx.doi.org/10.7150/jca.77322 |
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author | Wang, Chien-Hao Baskaran, Rathinasamy Ng, Shawn Shang-Chuan Wang, Tso-Fu Li, Chi-Cheng Ho, Tsung-Jung Hsieh, Dennis Jine-Yuan Kuo, Chia-Hua Chen, Ming-Cheng Huang, Chih-Yang |
author_facet | Wang, Chien-Hao Baskaran, Rathinasamy Ng, Shawn Shang-Chuan Wang, Tso-Fu Li, Chi-Cheng Ho, Tsung-Jung Hsieh, Dennis Jine-Yuan Kuo, Chia-Hua Chen, Ming-Cheng Huang, Chih-Yang |
author_sort | Wang, Chien-Hao |
collection | PubMed |
description | Oxaliplatin-based therapy is used as a first-line drug to treat metastatic colorectal cancer. However, long-term and repeated drug treatment resulted in drug resistance and the failure of chemotherapy. Various natural compounds were previously reported to act as chemosensitizers to reverse drug resistance. In this study, we found that platycodin D (PD), a saponin found in Platycodon grandiflorum, inhibited LoVo and OR-LoVo cells proliferation, invasion, and migration ability. Our results indicated that combined treatment of oxaliplatin with PD dramatically reduced the cellular proliferation in both LoVo and OR-LoVo cells. Furthermore, treatment with PD dose-dependently decreased LATS2/YAP1 hippo signaling and survival marker p-AKT expression, as well as increased cyclin-dependent kinase inhibitor proteins such as p21 and p27 expression. Importantly, PD activates and promotes YAP1 degradation through the ubiquitination and proteasome pathway. The nuclear transactivation of YAP was significantly reduced under PD treatment, leading to transcriptional inhibition of the downstream genes regulating cell proliferation, pro-survival, and metastasis. In conclusion, our results showed that PD is suitable as a promising agent for overcoming oxaliplatin-resistant colorectal cancer. |
format | Online Article Text |
id | pubmed-9969589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-99695892023-02-28 Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway Wang, Chien-Hao Baskaran, Rathinasamy Ng, Shawn Shang-Chuan Wang, Tso-Fu Li, Chi-Cheng Ho, Tsung-Jung Hsieh, Dennis Jine-Yuan Kuo, Chia-Hua Chen, Ming-Cheng Huang, Chih-Yang J Cancer Research Paper Oxaliplatin-based therapy is used as a first-line drug to treat metastatic colorectal cancer. However, long-term and repeated drug treatment resulted in drug resistance and the failure of chemotherapy. Various natural compounds were previously reported to act as chemosensitizers to reverse drug resistance. In this study, we found that platycodin D (PD), a saponin found in Platycodon grandiflorum, inhibited LoVo and OR-LoVo cells proliferation, invasion, and migration ability. Our results indicated that combined treatment of oxaliplatin with PD dramatically reduced the cellular proliferation in both LoVo and OR-LoVo cells. Furthermore, treatment with PD dose-dependently decreased LATS2/YAP1 hippo signaling and survival marker p-AKT expression, as well as increased cyclin-dependent kinase inhibitor proteins such as p21 and p27 expression. Importantly, PD activates and promotes YAP1 degradation through the ubiquitination and proteasome pathway. The nuclear transactivation of YAP was significantly reduced under PD treatment, leading to transcriptional inhibition of the downstream genes regulating cell proliferation, pro-survival, and metastasis. In conclusion, our results showed that PD is suitable as a promising agent for overcoming oxaliplatin-resistant colorectal cancer. Ivyspring International Publisher 2023-01-22 /pmc/articles/PMC9969589/ /pubmed/36860929 http://dx.doi.org/10.7150/jca.77322 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wang, Chien-Hao Baskaran, Rathinasamy Ng, Shawn Shang-Chuan Wang, Tso-Fu Li, Chi-Cheng Ho, Tsung-Jung Hsieh, Dennis Jine-Yuan Kuo, Chia-Hua Chen, Ming-Cheng Huang, Chih-Yang Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway |
title | Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway |
title_full | Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway |
title_fullStr | Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway |
title_full_unstemmed | Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway |
title_short | Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway |
title_sort | platycodin d confers oxaliplatin resistance in colorectal cancer by activating the lats2/yap1 axis of the hippo signaling pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969589/ https://www.ncbi.nlm.nih.gov/pubmed/36860929 http://dx.doi.org/10.7150/jca.77322 |
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