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

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。

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 IC50value 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.