减毒沙门菌SGN1对鼻咽癌的抑制作用及机制研究  

Prevention and inhibition of nasopharyngeal carcinoma growth by attenuated salmonella SGN1

作　　者：赖运浩 谭绮婷 黄庭祺 刘石 彭月荣 李芳红 赵正刚 周素瑾 麦家洛 赵子建 LAI Yun-hao;TAN Qi-ting;HUANG Ting-qi;LIU Shi;PENG Yue-rong;LI Fang-hong;ZHAO Zheng-gang;ZHOU Su-jin;MAI Jia-luo;ZHAO Zi-jian(School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China;School of Materials and Environment,Zhuhai College,Beijing Institute of Technology,Zhuhai Guangdong 519085,China;Guangzhou Sinogen Pharmaceutical Co.,Ltd.Guangzhou 510700,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006 [2]北京理工大学珠海学院材料与环境学院,广东珠海519085 [3]广州华津医药科技有限公司,广东广州510700

出　　处：《中国药理学通报》2023年第10期1867-1873,共7页Chinese Pharmacological Bulletin

基　　金：国家重点研发计划(No 2018YFA0800603);广东省重点领域研发计划“新药创制”专项(No 2019B020201015);广东省创新团队(No 2016ZT06ZT06Y432);基础与应用基础研究项目(No 202201010167)。

摘　　要：目的探讨高表达甲硫氨酸酶减毒沙门菌SGN1对鼻咽癌的抑制作用及其机制研究。方法通过甲硫氨酸限制培养,检测对人鼻咽癌细胞HNE-2、5-8F和CNE-2细胞增殖、迁移能力、克隆形成率以及细胞周期凋亡的影响;将SGN1与鼻咽癌细胞HNE-2、5-8F和CNE-2共培养,观察其增殖情况;构建5-8F人鼻咽癌细胞系皮下移植瘤模型,观察SGN1对体内鼻咽癌移植瘤的抑制作用;结果甲硫氨酸限制显著抑制鼻咽癌细胞的增殖、迁移能力、单克隆形成以及阻滞细胞周期G 2/M期并诱导细胞发生凋亡。SGN1能抑制鼻咽癌细胞的增殖并诱导凋亡,体内实验结果表明SGN1治疗后,小鼠皮下移植瘤生长受到抑制(P<0.05)。结论SGN1可促进鼻咽癌细胞发生凋亡且抑制肿瘤细胞迁移,为临床治疗提供一个新的治疗策略。Aim To study the inhibitory effect of attenuated salmonella SGN1,overexpressing methioninase,on nasopharyngeal carcinoma(NPC)and the underlying mechanism.Methods The cell proliferation,cell cycle,cell apoptosis,clony formation and migration ability of 5-8F,HNE-2,CNE-2 cells were measured using flow cytometry assay,clone formation assay,and wound assay after the methionine restriction treatment.5-8F,HNE-2,CNE-2 cells were infected with SGN1 at the multiplicity of infection(MOI)of 1∶100 for 5 hours,followed with the measurement of cell growth.A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma.Results Compared with the control group,methionine restriction significantly inhibited the proliferation,migration ability,and clone formation of nasopharyngeal carcinoma cells and blocked the G 2/M phase of cell cycle and induced apoptosis.SGN1 could inhibit the proliferation of nasopharyngeal carcinoma cells and induce apoptosis.In vivo experimental results indicated that the growth of xenograft tumors in mice was suppressed after SGN1 treatment(P<0.05).Conclusions SGN1 can promote the apoptosis of nasopharyngeal carcinoma cells and inhibit the migration of tumor cells,providing a potentially new therapeutic strategy for the clinical treatment of nasopharyngeal carcinoma.

关 键 词：减毒沙门菌 甲硫氨酸酶 SGN1 鼻咽癌 凋亡 细胞周期 

分 类 号：R-332[医药卫生] R329.25R329.28R378.22R739.63