LLY-283靶向PRMT5抑制头颈部鳞癌增殖和转移的实验研究

doi:10.19439/j.sjos.2022.02.006

上海口腔医学 ›› 2022, Vol. 31 ›› Issue (2): 142-147.doi: 10.19439/j.sjos.2022.02.006

LLY-283靶向PRMT5抑制头颈部鳞癌增殖和转移的实验研究

陈祺¹, 谢非², 季颖颖¹, 魏魁杰^1,*, 任强^1,*

1.复旦大学附属中山医院青浦分院口腔科,上海 201700;
2.上海交通大学附属第九人民医院口腔颌面-头颈肿瘤科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海 200011

收稿日期:2020-08-20 修回日期:2020-10-09 出版日期:2022-04-25 发布日期:2022-05-16
通讯作者: 任强,E-mail: rqking315@163.com;魏魁杰,E-mail: wkj100310@163.com。^*共同通信作者
作者简介:陈祺（1990-）,男,硕士,医师,E-mail:cqbbm20082019@163.com
基金资助:
上海市青浦区科学技术委员会发展基金项目（QKY2019-07）; 复旦大学附属中山医院青浦分院科研青年项目（QY2020-04）

LLY-283 inhibits proliferation and metastasis of head and neck squamous cell carcinoma by targeting PRMT5

CHEN Qi¹, XIE Fei², JI Ying-ying¹, WEI Kui-jie¹, REN Qiang¹

1. Department of Stomatology, Qingpu Branch of Zhongshan Hospital, Fudan University. Shanghai 201700;
2. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China

Received:2020-08-20 Revised:2020-10-09 Online:2022-04-25 Published:2022-05-16

摘要/Abstract

摘要： 目的： 探讨LLY-283通过蛋白质精氨酸甲基转移酶（protein arginine methyltransferase 5,PRMT5）对头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）增殖和转移生物学行为的影响。方法： 通过TCGA数据库、实时荧光定量PCR和免疫印迹实验检测PRMT5在HNSCC组织、细胞系中表达水平;利用慢病毒技术构建PRMT5敲低稳转细胞株,分析PRMT5对HNSCC细胞生物学行为影响,药物杀伤实验观察LLY-283在细胞系中IC50变化;细胞实验和裸鼠移植瘤实验进一步检测LLY-283通过PRMT5对HNSCC生物学作用。结果： PRMT5在HNSCC组织和细胞系中高表达,促进HNSCC增殖和转移能力,降低药物LLY-283的IC₅₀值。LLY-283可通过PRMT5显著降低HNSCC增殖和转移能力、体内裸鼠移植瘤体积和Ki-67表达量。结论： LLY-283可能通过抑制PRMT5和Ki-67表达,降低HNSCC增殖、转移和裸鼠移植瘤形成能力,发挥抗肿瘤作用。

关键词: 头颈部鳞癌, PRMT5, LLY-283, 细胞增殖

Abstract: PURPOSE: To explore the effect of LLY-283 on the biological behavior of Head and neck squamous cell carcinoma(HNSCC) proliferation and metastasis through protein arginine methyltransferase 5(PRMT5). METHODS: TCGA database was used to analyze the expression level of PRMT5 in HNSCC tissues and cell lines by RT-PCR and Western blot. Lentiviral technology was used to construct PRMT5 knockdown stable cell line, and analyze the effect of PRMT5 on the biological behavior of HNSCC. Drug killing experiment was used to observe the IC50 changes of LLY-283 in cell lines. Nude mouse xenograft experiments were further tested to observe the biological effects of LLY-283 on HNSCC through PRMT5. RESULTS: PRMT5 was highly expressed in HNSCC tissues and cell lines, which promoted the proliferation and metastasis of cell lines, and reduced the IC₅₀ value of LLY-283. LLY-283 could significantly reduce the cell proliferation and metastasis, tumor volume and Ki-67 expression in nude mice in vivo of HNSCC through PRMT5. CONCLUSIONS: LLY-283 inhibits the expression of PRMT5 and Ki-67, thereby decreases the proliferation and metastasis of HNSCC and the ability to form transplanted tumors in nude mice, exerting anti-tumor effects.

Key words: Head and neck squamous cell carcinoma, PRMT5, LLY-283, Cell proliferation

中图分类号:

R739.8

陈祺, 谢非, 季颖颖, 魏魁杰, 任强. LLY-283靶向PRMT5抑制头颈部鳞癌增殖和转移的实验研究[J]. 上海口腔医学, 2022, 31(2): 142-147.

CHEN Qi, XIE Fei, JI Ying-ying, WEI Kui-jie, REN Qiang. LLY-283 inhibits proliferation and metastasis of head and neck squamous cell carcinoma by targeting PRMT5[J]. Shanghai Journal of Stomatology, 2022, 31(2): 142-147.

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LLY-283靶向PRMT5抑制头颈部鳞癌增殖和转移的实验研究

LLY-283 inhibits proliferation and metastasis of head and neck squamous cell carcinoma by targeting PRMT5

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