Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5

AIM: To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and oridonin on choroidal melanoma cell lines, and to explore its underlying mechanism. METHODS: MUM-2B and C918 cells were treated with different concentrations of TRAIL...

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Autores principales:	Xin Hua, Peng Wu, Guo-Sheng Gao, Xiao-Lei Ye
Formato:	article
Lenguaje:	EN
Publicado:	Press of International Journal of Ophthalmology (IJO PRESS) 2021
Materias:	tumor necrosis factor-related apoptosis-inducing ligand oridonin apoptosis choroidal melanoma Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/abe1a0986db0458c8b888d05c273f0e2
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spelling	oai:doaj.org-article:abe1a0986db0458c8b888d05c273f0e22021-11-26T04:02:12ZCombination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR52222-39592227-489810.18240/ijo.2021.12.05https://doaj.org/article/abe1a0986db0458c8b888d05c273f0e22021-12-01T00:00:00Zhttp://ies.ijo.cn/en_publish/2021/12/20211205.pdfhttps://doaj.org/toc/2222-3959https://doaj.org/toc/2227-4898AIM: To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and oridonin on choroidal melanoma cell lines, and to explore its underlying mechanism. METHODS: MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin, and MTT assay used to evaluate the inhibition rate of the two compounds on cells. Then, the cell cycle distribution and apoptosis were detected by flow cytometry, and changes in apoptosis-related proteins such as death receptor 5 (DR5), a-caspase-3, and x-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot. MUM-2B cells were transfected with si-DR5, which interfered with the expression of the DR5 gene. MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins. RESULTS: When TRAIL and oridonin were simultaneously administered to the MUM-2B cells, the apoptosis rate was significantly higher than that by the two drugs individually. However, the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone. Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells. The Western blot results showed that the protein expression levels of the DR5, a-caspase-3, and BAX increased, while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells. Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells. CONCLUSION: The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment, which may ascribe to up-regulation of DR5.Xin HuaPeng WuGuo-Sheng GaoXiao-Lei YePress of International Journal of Ophthalmology (IJO PRESS)articletumor necrosis factor-related apoptosis-inducing ligandoridoninapoptosischoroidal melanomaOphthalmologyRE1-994ENInternational Journal of Ophthalmology, Vol 14, Iss 12, Pp 1834-1842 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor necrosis factor-related apoptosis-inducing ligand oridonin apoptosis choroidal melanoma Ophthalmology RE1-994
spellingShingle	tumor necrosis factor-related apoptosis-inducing ligand oridonin apoptosis choroidal melanoma Ophthalmology RE1-994 Xin Hua Peng Wu Guo-Sheng Gao Xiao-Lei Ye Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5
description	AIM: To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and oridonin on choroidal melanoma cell lines, and to explore its underlying mechanism. METHODS: MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin, and MTT assay used to evaluate the inhibition rate of the two compounds on cells. Then, the cell cycle distribution and apoptosis were detected by flow cytometry, and changes in apoptosis-related proteins such as death receptor 5 (DR5), a-caspase-3, and x-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot. MUM-2B cells were transfected with si-DR5, which interfered with the expression of the DR5 gene. MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins. RESULTS: When TRAIL and oridonin were simultaneously administered to the MUM-2B cells, the apoptosis rate was significantly higher than that by the two drugs individually. However, the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone. Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells. The Western blot results showed that the protein expression levels of the DR5, a-caspase-3, and BAX increased, while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells. Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells. CONCLUSION: The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment, which may ascribe to up-regulation of DR5.
format	article
author	Xin Hua Peng Wu Guo-Sheng Gao Xiao-Lei Ye
author_facet	Xin Hua Peng Wu Guo-Sheng Gao Xiao-Lei Ye
author_sort	Xin Hua
title	Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5
title_short	Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5
title_full	Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5
title_fullStr	Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5
title_full_unstemmed	Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5
title_sort	combination of oridonin and trail induces apoptosis in uveal melanoma cells by upregulating dr5
publisher	Press of International Journal of Ophthalmology (IJO PRESS)
publishDate	2021
url	https://doaj.org/article/abe1a0986db0458c8b888d05c273f0e2
work_keys_str_mv	AT xinhua combinationoforidoninandtrailinducesapoptosisinuvealmelanomacellsbyupregulatingdr5 AT pengwu combinationoforidoninandtrailinducesapoptosisinuvealmelanomacellsbyupregulatingdr5 AT guoshenggao combinationoforidoninandtrailinducesapoptosisinuvealmelanomacellsbyupregulatingdr5 AT xiaoleiye combinationoforidoninandtrailinducesapoptosisinuvealmelanomacellsbyupregulatingdr5
_version_	1718409921257537536

Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5

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