中国肿瘤生物治疗杂志2024，Vol.31Issue(6)：586-591,6.DOI:10.3872/j.issn.1007-385x.2024.06.007
SETD5介导AKT1磷酸化调控结肠癌细胞的迁移和5-FU敏感性
SETD5 regulates colon cancer cell migration and 5-FU sensitivity by mediating AKT1 phosphorylation
摘要
Abstract
Objective:To investigate the effect of SET domain-containing 5(SETD5)on the proliferation,migration and 5-fluorouracil(5-FU)drug sensitivity of colon cancer cells and its mechanism.Methods:Colon cancer cells were cultured routinely,and siSETD5-NC and si-SETD5-1-3 plasmids were transfected into HT-29 cells with Lipofectamine 2000.The cells were divided into the control group(untreated),the si-SETD5-NC group,the si-SETD5 group and the si-SETD5+SC79 group.The HT-29 cells in the si-SETD5+SC79 group were transfected with plasmids and treated simultaneously with 10 µmol/L SC79.SETD5 mRNA expression in NCM460,HT-29 and LoVo cells was detected by qPCR.Flow cytometry,cell scratch method,WB method and CCK-8 method were used to detect the apoptosis,migration ability,expression of related proteins and sensitivity to 5-FU of HT-29 cells in each group,respectively.Results:SETD5 mRNA was highly expressed in both HT-29 and LoVo cells(both P<0.01).SETD5 mRNA was successfully knocked down in HT-29 cells(P<0.01).Knockdown of SETD5 mRNA could significantly inhibit the proliferation activity(P<0.01),migration ability(P<0.01),expression of related proteins(SETD5,p-PI3K,p-AKT1,p-mTOR protein)of HT-29 cells(all P<0.01),promote apoptosis(P<0.01),and increase the sensitivity to 5-FU(P<0.01).These effects could be partially blocked by AKT activator SC79(P<0.05 or P<0.01).Conclusion:SETD5 is highly expressed in HT-29 and LoVo cells.SETD5 promotes the proliferation and migration of colon cancer HT-29 cells and reduces sensitivity to 5-FU through PI3K/AKT1 pathway.SETD5 is a potential target for clinical diagnosis and treatment of colon cancer.关键词
结肠癌/含有SET结构域蛋白5/蛋白激酶B磷酸化/增殖/迁移/5-氟尿嘧啶/耐药Key words
colon cancer/SET domain-containing 5(SETD5)/protein kinase B phosphorylation/proliferation/migration/5-fluorouracil(5-Fu)/drug resistance分类
医药卫生引用本文复制引用
黄开禹,史建国,程勇..SETD5介导AKT1磷酸化调控结肠癌细胞的迁移和5-FU敏感性[J].中国肿瘤生物治疗杂志,2024,31(6):586-591,6.基金项目
2021年武汉市中心医院学科基金项目(No.2021XK063) （No.2021XK063）
