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Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway

Melanoma is a common skin tumor that causes a high rate of mortality, especially in Europe, North America and Oceania. Immunosuppressants such as anti-PD-1 have been used in the treatment of malignant melanoma, however, nearly 60% of patients do not respond to these treatments. Sema4D, also called C...

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Autores principales: Zhang, Zhuo, Zhang, Duoli, Wang, Fang, Liu, Jiao, Sun, Yuhong, Anuchapreeda, Songyot, Tima, Singkome, Xiao, Zhangang, Duangmano, Suwit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122458/
https://www.ncbi.nlm.nih.gov/pubmed/37096066
http://dx.doi.org/10.7717/peerj.15172
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author Zhang, Zhuo
Zhang, Duoli
Wang, Fang
Liu, Jiao
Sun, Yuhong
Anuchapreeda, Songyot
Tima, Singkome
Xiao, Zhangang
Duangmano, Suwit
author_facet Zhang, Zhuo
Zhang, Duoli
Wang, Fang
Liu, Jiao
Sun, Yuhong
Anuchapreeda, Songyot
Tima, Singkome
Xiao, Zhangang
Duangmano, Suwit
author_sort Zhang, Zhuo
collection PubMed
description Melanoma is a common skin tumor that causes a high rate of mortality, especially in Europe, North America and Oceania. Immunosuppressants such as anti-PD-1 have been used in the treatment of malignant melanoma, however, nearly 60% of patients do not respond to these treatments. Sema4D, also called CD100, is expressed in T cells and tumor tissues. Sema4D and its receptor, Plexin-B1, play crucial roles in the process of immune regulation, angiogenesis, and tumor progression. The role of Sema4D in melanoma with anti-PD-1 resistance is poorly understood. Through a combination of molecular biology techniques and in silico analysis, the role of Sema4D in improving anti-PD-L1 sensitivity in melanoma was explored. The results showed that the expression of Sema4D, Plexin-B1 and PD-L1 was significantly increased in B16-F10R cells. Sema4D knockdown synergizes with anti-PD-1 treatment, cell viability, cell invasion and migration were significantly decreased, while the apoptosis was increased, the growth of tumors on the mice was also inhibited. Mechanistically, bioinformatics analysis revealed that Sema4D is involved in the PI3K/AKT signaling pathway; the downregulation of p-PI3K/PI3K and p-AKT/AKT expression were observed in Sema4D knockdown, therefore, nivolumab resistance is related to Sema4D and Sema4D silencing can improve sensitivity to nivolumab via inhibition of the PI3K/AKT signaling pathway.
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spelling pubmed-101224582023-04-23 Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway Zhang, Zhuo Zhang, Duoli Wang, Fang Liu, Jiao Sun, Yuhong Anuchapreeda, Songyot Tima, Singkome Xiao, Zhangang Duangmano, Suwit PeerJ Biochemistry Melanoma is a common skin tumor that causes a high rate of mortality, especially in Europe, North America and Oceania. Immunosuppressants such as anti-PD-1 have been used in the treatment of malignant melanoma, however, nearly 60% of patients do not respond to these treatments. Sema4D, also called CD100, is expressed in T cells and tumor tissues. Sema4D and its receptor, Plexin-B1, play crucial roles in the process of immune regulation, angiogenesis, and tumor progression. The role of Sema4D in melanoma with anti-PD-1 resistance is poorly understood. Through a combination of molecular biology techniques and in silico analysis, the role of Sema4D in improving anti-PD-L1 sensitivity in melanoma was explored. The results showed that the expression of Sema4D, Plexin-B1 and PD-L1 was significantly increased in B16-F10R cells. Sema4D knockdown synergizes with anti-PD-1 treatment, cell viability, cell invasion and migration were significantly decreased, while the apoptosis was increased, the growth of tumors on the mice was also inhibited. Mechanistically, bioinformatics analysis revealed that Sema4D is involved in the PI3K/AKT signaling pathway; the downregulation of p-PI3K/PI3K and p-AKT/AKT expression were observed in Sema4D knockdown, therefore, nivolumab resistance is related to Sema4D and Sema4D silencing can improve sensitivity to nivolumab via inhibition of the PI3K/AKT signaling pathway. PeerJ Inc. 2023-04-19 /pmc/articles/PMC10122458/ /pubmed/37096066 http://dx.doi.org/10.7717/peerj.15172 Text en ©2023 Zhang et al. 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/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Zhang, Zhuo
Zhang, Duoli
Wang, Fang
Liu, Jiao
Sun, Yuhong
Anuchapreeda, Songyot
Tima, Singkome
Xiao, Zhangang
Duangmano, Suwit
Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway
title Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway
title_full Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway
title_fullStr Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway
title_full_unstemmed Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway
title_short Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway
title_sort sema4d silencing increases the sensitivity of nivolumab to b16-f10 resistant melanoma via inhibiting the pi3k/akt signaling pathway
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122458/
https://www.ncbi.nlm.nih.gov/pubmed/37096066
http://dx.doi.org/10.7717/peerj.15172
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