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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PeerJ Inc.
2023-04-01
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| author | Zhuo Zhang Duoli Zhang Fang Wang Jiao Liu Yuhong Sun Songyot Anuchapreeda Singkome Tima Zhangang Xiao Suwit Duangmano |
| author_facet | Zhuo Zhang Duoli Zhang Fang Wang Jiao Liu Yuhong Sun Songyot Anuchapreeda Singkome Tima Zhangang Xiao Suwit Duangmano |
| author_sort | Zhuo Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T06:51:59Z |
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| last_indexed | 2024-03-09T06:51:59Z |
| publishDate | 2023-04-01 |
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| spelling | doaj.art-4d721755a94046f9b8db78cd72c6dc012023-12-03T10:24:15ZengPeerJ Inc.PeerJ2167-83592023-04-0111e1517210.7717/peerj.15172Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathwayZhuo Zhang0Duoli Zhang1Fang Wang2Jiao Liu3Yuhong Sun4Songyot Anuchapreeda5Singkome Tima6Zhangang Xiao7Suwit Duangmano8Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandDepartment of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandMelanoma 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.https://peerj.com/articles/15172.pdfSema4DMelanomaNivolumabPI3K/AKTPD-1 inhibitor resistance |
| spellingShingle | Zhuo Zhang Duoli Zhang Fang Wang Jiao Liu Yuhong Sun Songyot Anuchapreeda Singkome Tima Zhangang Xiao Suwit Duangmano Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway PeerJ Sema4D Melanoma Nivolumab PI3K/AKT PD-1 inhibitor resistance |
| 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 | Sema4D Melanoma Nivolumab PI3K/AKT PD-1 inhibitor resistance |
| url | https://peerj.com/articles/15172.pdf |
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