HS3ST1对肺癌细胞增殖、迁移、侵袭及顺铂耐药的作用机制研究

目的:研究HS3ST1对肺癌细胞A549增殖、迁移、侵袭及顺铂耐药的影响。方法:利用慢病毒感染并构建HS3ST1过表达细胞株;利用Western blot、RT-PCT检测HS3ST1的表达;利用CCK8实验、Transwell迁移实验和细胞毒性实验检测HS3ST1对A549细胞增殖、迁移、侵袭和顺铂耐药的影响;利用Western blot检测NF-κB信号通路的蛋白改变;利用GEO数据库（GSE108214）进行顺铂耐药基因分析，利用GEO数据库（GSE30219）数据分析HS3ST1表达水平对肺癌患者总生存时间（overall survival，OS）的影响。结果:HS3ST1在肺癌细胞及肺癌组织中呈高表达，中晚期（Ⅲ-Ⅳ期）肺癌组织中HS3ST1表达高于早期（Ⅰ-Ⅱ期）肺癌组织;过表达HS3ST1促进A549细胞的增殖、迁移和侵袭;GEO数据库（GSE108214）分析显示顺铂耐药细胞株高表达HS3ST1;细胞毒性实验表明过表达HS3ST1导致肺癌细胞顺铂耐药;过表达HS3ST1活化p65及p-p65;GEO数据库（GSE30219）数据显示高表达HS3ST1肺癌患者OS显著缩短。结论:HS3ST1可能通过NF-κB信号通路促进肺癌细胞的增殖、迁移、侵袭及顺铂耐药，高表达HS3ST1肺癌患者预后较差。

Effects of HS3ST1 on proliferation,migration,invasion and cisplatin resistance of lung cancer cell

Objective:To study the effects of HS3ST1 on proliferation,migration,invasion and cisplatin resistance of lung cancer cell line.Methods:HS3ST1 overexpression cell line was constructed by lentivirus infection.The expression of HS3ST1 was detected by RT-PCT and Western blot.The effects of HS3ST1 overexpression on proliferation,migration,invasion and cisplatin resistance of A549 cells were detected by CCK8 test,Transwell test,Invsion test and cytotoxicity test.Proteins in NF-κB pathway were evaluated by Western blot.The GEO database(GSE108214)was used for cisplatin resistance analysis,and the GEO database(GSE30219)data was used to analyze the effect of HS3ST1 expression on the survival time of patients with lung cancer.Results:The expression of HS3ST1 was higher in lung cancer cells and lung cancer tissues,compared to normal lung cells and non-cancer lung tissues.The expression of HS3ST1 in middle and late stage(Ⅲ-Ⅳstage)was higher than that in early stage(Ⅰ-Ⅱstage).Overexpression of HS3ST1 promoted the proliferation,migration and invasion of A549 cells.GEO database(GSE108214)analysis showed that cisplatin resistant cell lines highly expressed HS3ST1.Cytotoxicity assay showed that overexpression of HS3ST1 led to cisplatin resistance in lung cancer cells.GEO database(GSE30219)data showed that the total survival time of lung cancer patients with high expression of HS3ST1 was significantly shortened.Conclusion:HS3ST1 promoted the proliferation,migration,invasion and cisplatin resistance of lung cancer cells by activating NF-κB signaling pathway,and the prognosis of lung cancer patients with higher expression of HS3ST1 is significantly poor than those with lower expression of HS3ST1.