To explore immune synergistic function of Quercetin in inhibiting breast cancer cells

Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class...

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Autores principales:	Dan Qiu, Xianxin Yan, Xinqin Xiao, Guijuan Zhang, Yanqiu Wang, Jingyu Cao, Ruirui Ma, Shouyi Hong, Min Ma
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Que Breast cancer Breast precancerous lesion γδ T cell JAK/STAT1 signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/d74e25fa5f7b4a2896719c289f3f17f2
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spelling	oai:doaj.org-article:d74e25fa5f7b4a2896719c289f3f17f22021-11-28T12:36:59ZTo explore immune synergistic function of Quercetin in inhibiting breast cancer cells10.1186/s12935-021-02345-51475-2867https://doaj.org/article/d74e25fa5f7b4a2896719c289f3f17f22021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02345-5https://doaj.org/toc/1475-2867Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells. Methods In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h. Results The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P < 0.05). Most importantly, Que promoted the differentiation of γδ T cells into the Vδ2 T cell subpopulation. The best ratio of effector cells to target cells (E/T) was 10:1, the killing percentages of γδ T cells against MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 were 61.44 ± 4.70, 55.52 ± 3.10, 53.94 ± 2.74, and 53.28 ± 1.73 (P = 0.114, P = 0.486, and P = 0.343, respectively), and the strongest killing effect on precancerous breast cancer cells and breast cancer cells was found when the Que concentration was 5 μM and the E/T ratio was 10:1 (64.94 ± 3.61, 64.96 ± 5.45, 55.59 ± 5.98, and 59.04 ± 5.67, respectively). In addition, our results showed that Que increased the protein levels of IFNγ-R, p-JAK2 and p-STAT1 while decreasing the protein levels of PD-L1 (P < 0.0001). Conclusions In conclusion, Que plays a synergistic role in killing breast cancer cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1 and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of breast cancer.Dan QiuXianxin YanXinqin XiaoGuijuan ZhangYanqiu WangJingyu CaoRuirui MaShouyi HongMin MaBMCarticleQueBreast cancerBreast precancerous lesionγδ T cellJAK/STAT1 signaling pathwayNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Que Breast cancer Breast precancerous lesion γδ T cell JAK/STAT1 signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Que Breast cancer Breast precancerous lesion γδ T cell JAK/STAT1 signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Dan Qiu Xianxin Yan Xinqin Xiao Guijuan Zhang Yanqiu Wang Jingyu Cao Ruirui Ma Shouyi Hong Min Ma To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
description	Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells. Methods In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h. Results The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P < 0.05). Most importantly, Que promoted the differentiation of γδ T cells into the Vδ2 T cell subpopulation. The best ratio of effector cells to target cells (E/T) was 10:1, the killing percentages of γδ T cells against MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 were 61.44 ± 4.70, 55.52 ± 3.10, 53.94 ± 2.74, and 53.28 ± 1.73 (P = 0.114, P = 0.486, and P = 0.343, respectively), and the strongest killing effect on precancerous breast cancer cells and breast cancer cells was found when the Que concentration was 5 μM and the E/T ratio was 10:1 (64.94 ± 3.61, 64.96 ± 5.45, 55.59 ± 5.98, and 59.04 ± 5.67, respectively). In addition, our results showed that Que increased the protein levels of IFNγ-R, p-JAK2 and p-STAT1 while decreasing the protein levels of PD-L1 (P < 0.0001). Conclusions In conclusion, Que plays a synergistic role in killing breast cancer cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1 and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of breast cancer.
format	article
author	Dan Qiu Xianxin Yan Xinqin Xiao Guijuan Zhang Yanqiu Wang Jingyu Cao Ruirui Ma Shouyi Hong Min Ma
author_facet	Dan Qiu Xianxin Yan Xinqin Xiao Guijuan Zhang Yanqiu Wang Jingyu Cao Ruirui Ma Shouyi Hong Min Ma
author_sort	Dan Qiu
title	To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
title_short	To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
title_full	To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
title_fullStr	To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
title_full_unstemmed	To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
title_sort	to explore immune synergistic function of quercetin in inhibiting breast cancer cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d74e25fa5f7b4a2896719c289f3f17f2
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To explore immune synergistic function of Quercetin in inhibiting breast cancer cells

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