Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling

Qian Jiang,1– 3 Nan Zhang,2 Xin Li,2 Wei Hou,4 Xiao-Qing Zhao,5 Lei Liu1,2 1Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China; 2State Key Laboratory of Biotherapy, Wes...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jiang Q, Zhang N, Li X, Hou W, Zhao XQ, Liu L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	lung cancer dl-3-n-butylphthalide kat7 pd-1/pd-l1 axis immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ee94fc8d7d034543a39fa7a3022f1b3b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ee94fc8d7d034543a39fa7a3022f1b3b
record_format	dspace
spelling	oai:doaj.org-article:ee94fc8d7d034543a39fa7a3022f1b3b2021-11-11T18:22:26ZDl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling1179-1322https://doaj.org/article/ee94fc8d7d034543a39fa7a3022f1b3b2021-11-01T00:00:00Zhttps://www.dovepress.com/dl-3-n-butylphthalide-presents-anti-cancer-activity-in-lung-cancer-by--peer-reviewed-fulltext-article-CMARhttps://doaj.org/toc/1179-1322Qian Jiang,1– 3 Nan Zhang,2 Xin Li,2 Wei Hou,4 Xiao-Qing Zhao,5 Lei Liu1,2 1Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China; 2State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, 637000, Sichuan, People’s Republic of China; 4Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, 637000, Sichuan, People’s Republic of China; 5Department of Oncology, The Second Affiliated Hospital of North Sichuan Medical College, Nan Chong, 637000, Sichuan, People’s Republic of ChinaCorrespondence: Lei Liu Email liuleihx@gmail.comIntroduction: Lung cancer serves as one of the most malignant cancer types. Immunotherapy targeting PD-1/PD-L1 axis is a promising strategy for cancer treatment. Dl-3-N-butylphthalide (NBP), a small molecule compound extracted from the seeds of Apium graveolens, possesses a large range of biological effects and demonstrates anti-cancer activities. However, the role of NBP in the modulation of lung cancer remains obscure.Methods: In this study, we aimed to explore the effect of NBP on PD-L1 signaling and the progression of lung cancer.Results: Significantly, the treatment of NBP repressed the proliferation of lung cancer cells in vitro. Tumorigenicity analysis in nude mice showed that the tumor volume and tumor weight were attenuated by the treatment of NBP in the mice. Meanwhile, the levels of Ki-67 and PD-L1 were reduced by the treatment of NBP in the tumor tissues of the mice. NBP suppressed IFN-γ-induced PD-L1 enhancement in lung cancer cells. The treatment of NBP inhibited PD-L1 expression in lung cancer cells co-cultured with unstimulated PBMCs or activated T cell. NBP inhibited PD-1 expression in activated T cells co-cultured with lung cancer cells. Conditioned medium from activated T cells increased PD-L1 expression, and NBP reversed this effect. Co-culture with A549 and H1975 cells reduced T cell proliferation and activity, while the treatment of NBP reversed the reduction. Consistently, the treatment of NBP caused notably decreased apoptosis of co-cultured T cells. Mechanically, KAT7 was able to bind to PD-L1 promoter and epigenetically induce PD-L1 expression by promoting the enrichment of histone H3 lysine 14 acetylation (H3K14ac) and RNA polymerase II on PD-L1 promoter.Discussion: Thus, we concluded that NBP repressed PD-L1 expression by targeting KAT7 and attenuated PD-1/PD-L1 axis to relieve lung cancer progression. NBP may be applied as the potential therapeutic strategy in immunotherapy of lung cancer.Keywords: lung cancer, Dl-3-N-butylphthalide, KAT7, PD-1/PD-L1 axis, immunotherapyJiang QZhang NLi XHou WZhao XQLiu LDove Medical Pressarticlelung cancerdl-3-n-butylphthalidekat7pd-1/pd-l1 axisimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Management and Research, Vol Volume 13, Pp 8513-8524 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lung cancer dl-3-n-butylphthalide kat7 pd-1/pd-l1 axis immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	lung cancer dl-3-n-butylphthalide kat7 pd-1/pd-l1 axis immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jiang Q Zhang N Li X Hou W Zhao XQ Liu L Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling
description	Qian Jiang,1– 3 Nan Zhang,2 Xin Li,2 Wei Hou,4 Xiao-Qing Zhao,5 Lei Liu1,2 1Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China; 2State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, 637000, Sichuan, People’s Republic of China; 4Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, 637000, Sichuan, People’s Republic of China; 5Department of Oncology, The Second Affiliated Hospital of North Sichuan Medical College, Nan Chong, 637000, Sichuan, People’s Republic of ChinaCorrespondence: Lei Liu Email liuleihx@gmail.comIntroduction: Lung cancer serves as one of the most malignant cancer types. Immunotherapy targeting PD-1/PD-L1 axis is a promising strategy for cancer treatment. Dl-3-N-butylphthalide (NBP), a small molecule compound extracted from the seeds of Apium graveolens, possesses a large range of biological effects and demonstrates anti-cancer activities. However, the role of NBP in the modulation of lung cancer remains obscure.Methods: In this study, we aimed to explore the effect of NBP on PD-L1 signaling and the progression of lung cancer.Results: Significantly, the treatment of NBP repressed the proliferation of lung cancer cells in vitro. Tumorigenicity analysis in nude mice showed that the tumor volume and tumor weight were attenuated by the treatment of NBP in the mice. Meanwhile, the levels of Ki-67 and PD-L1 were reduced by the treatment of NBP in the tumor tissues of the mice. NBP suppressed IFN-γ-induced PD-L1 enhancement in lung cancer cells. The treatment of NBP inhibited PD-L1 expression in lung cancer cells co-cultured with unstimulated PBMCs or activated T cell. NBP inhibited PD-1 expression in activated T cells co-cultured with lung cancer cells. Conditioned medium from activated T cells increased PD-L1 expression, and NBP reversed this effect. Co-culture with A549 and H1975 cells reduced T cell proliferation and activity, while the treatment of NBP reversed the reduction. Consistently, the treatment of NBP caused notably decreased apoptosis of co-cultured T cells. Mechanically, KAT7 was able to bind to PD-L1 promoter and epigenetically induce PD-L1 expression by promoting the enrichment of histone H3 lysine 14 acetylation (H3K14ac) and RNA polymerase II on PD-L1 promoter.Discussion: Thus, we concluded that NBP repressed PD-L1 expression by targeting KAT7 and attenuated PD-1/PD-L1 axis to relieve lung cancer progression. NBP may be applied as the potential therapeutic strategy in immunotherapy of lung cancer.Keywords: lung cancer, Dl-3-N-butylphthalide, KAT7, PD-1/PD-L1 axis, immunotherapy
format	article
author	Jiang Q Zhang N Li X Hou W Zhao XQ Liu L
author_facet	Jiang Q Zhang N Li X Hou W Zhao XQ Liu L
author_sort	Jiang Q
title	Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling
title_short	Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling
title_full	Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling
title_fullStr	Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling
title_full_unstemmed	Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling
title_sort	dl-3-n-butylphthalide presents anti-cancer activity in lung cancer by targeting pd-1/pd-l1 signaling
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/ee94fc8d7d034543a39fa7a3022f1b3b
work_keys_str_mv	AT jiangq dl3nbutylphthalidepresentsanticanceractivityinlungcancerbytargetingpd1pdl1signaling AT zhangn dl3nbutylphthalidepresentsanticanceractivityinlungcancerbytargetingpd1pdl1signaling AT lix dl3nbutylphthalidepresentsanticanceractivityinlungcancerbytargetingpd1pdl1signaling AT houw dl3nbutylphthalidepresentsanticanceractivityinlungcancerbytargetingpd1pdl1signaling AT zhaoxq dl3nbutylphthalidepresentsanticanceractivityinlungcancerbytargetingpd1pdl1signaling AT liul dl3nbutylphthalidepresentsanticanceractivityinlungcancerbytargetingpd1pdl1signaling
_version_	1718431857344774144

Dl-3-N-Butylphthalide Presents Anti-Cancer Activity in Lung Cancer by Targeting PD-1/PD-L1 Signaling

Ejemplares similares