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Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway

Cetuximab is a monoclonal antibody against epidermal growth factor receptor that blocks downstream signaling pathways of receptor tyrosine kinases, including Ras/Raf/MAPK and PI3K/Akt, thereby inhibiting tumor cell proliferation and inducing cancer cell apoptosis. Owing to KRAS mutations, the effect...

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Autores principales: Liu, Yanfei, Tian, Shifeng, Yi, Ben, Feng, Zhiqiang, Chu, Tianhao, Liu, Jun, Zhang, Chunze, Zhang, Shiwu, Wang, Yijia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646952/
https://www.ncbi.nlm.nih.gov/pubmed/36387129
http://dx.doi.org/10.3389/fonc.2022.1046143
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author Liu, Yanfei
Tian, Shifeng
Yi, Ben
Feng, Zhiqiang
Chu, Tianhao
Liu, Jun
Zhang, Chunze
Zhang, Shiwu
Wang, Yijia
author_facet Liu, Yanfei
Tian, Shifeng
Yi, Ben
Feng, Zhiqiang
Chu, Tianhao
Liu, Jun
Zhang, Chunze
Zhang, Shiwu
Wang, Yijia
author_sort Liu, Yanfei
collection PubMed
description Cetuximab is a monoclonal antibody against epidermal growth factor receptor that blocks downstream signaling pathways of receptor tyrosine kinases, including Ras/Raf/MAPK and PI3K/Akt, thereby inhibiting tumor cell proliferation and inducing cancer cell apoptosis. Owing to KRAS mutations, the effectiveness of cetuximab is usually limited by intrinsic drug resistance. Continuous activation of the PI3K/Akt signaling pathway is another reason for cetuximab resistance. Platycodin-D, a bioactive compound isolated from the Chinese herb Platycodon grandiflorum, regulates Akt in different trends based on tissue types. To investigate whether platycodin-D can sensitize KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway, HCT116 and LoVo cells were treated with cetuximab and platycodin-D. LY294002 and SC79 were used to regulate Akt to further evaluate whether platycodin-D sensitizes cells to cetuximab by inhibiting Akt. Our results confirmed that platycodin-D increased the cytotoxic effects of cetuximab, including inhibition of growth, migration, and invasion, via downregulation of PI3K and Akt phosphorylation in HCT116 and LoVo cells both in vitro and in vivo. Given these data, platycodin-D may sensitize KRAS-mutant colorectal cancer cells to cetuximab via inhibition of the PI3K/Akt signaling pathway.
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spelling pubmed-96469522022-11-15 Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway Liu, Yanfei Tian, Shifeng Yi, Ben Feng, Zhiqiang Chu, Tianhao Liu, Jun Zhang, Chunze Zhang, Shiwu Wang, Yijia Front Oncol Oncology Cetuximab is a monoclonal antibody against epidermal growth factor receptor that blocks downstream signaling pathways of receptor tyrosine kinases, including Ras/Raf/MAPK and PI3K/Akt, thereby inhibiting tumor cell proliferation and inducing cancer cell apoptosis. Owing to KRAS mutations, the effectiveness of cetuximab is usually limited by intrinsic drug resistance. Continuous activation of the PI3K/Akt signaling pathway is another reason for cetuximab resistance. Platycodin-D, a bioactive compound isolated from the Chinese herb Platycodon grandiflorum, regulates Akt in different trends based on tissue types. To investigate whether platycodin-D can sensitize KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway, HCT116 and LoVo cells were treated with cetuximab and platycodin-D. LY294002 and SC79 were used to regulate Akt to further evaluate whether platycodin-D sensitizes cells to cetuximab by inhibiting Akt. Our results confirmed that platycodin-D increased the cytotoxic effects of cetuximab, including inhibition of growth, migration, and invasion, via downregulation of PI3K and Akt phosphorylation in HCT116 and LoVo cells both in vitro and in vivo. Given these data, platycodin-D may sensitize KRAS-mutant colorectal cancer cells to cetuximab via inhibition of the PI3K/Akt signaling pathway. Frontiers Media S.A. 2022-10-27 /pmc/articles/PMC9646952/ /pubmed/36387129 http://dx.doi.org/10.3389/fonc.2022.1046143 Text en Copyright © 2022 Liu, Tian, Yi, Feng, Chu, Liu, Zhang, Zhang and Wang https://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 Oncology
Liu, Yanfei
Tian, Shifeng
Yi, Ben
Feng, Zhiqiang
Chu, Tianhao
Liu, Jun
Zhang, Chunze
Zhang, Shiwu
Wang, Yijia
Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway
title Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway
title_full Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway
title_fullStr Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway
title_full_unstemmed Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway
title_short Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway
title_sort platycodin d sensitizes kras-mutant colorectal cancer cells to cetuximab by inhibiting the pi3k/akt signaling pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646952/
https://www.ncbi.nlm.nih.gov/pubmed/36387129
http://dx.doi.org/10.3389/fonc.2022.1046143
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