叉头框家族D3和腺苷酸活化蛋白激酶5与胃癌顺铂耐药机制的研究  

Mechanism of forkhead box D3 and AMPK-related kinase 5 involved in the cisplatin resistance in gastric cancer

作　　者：王慧[1] 顾康生[1] WANG Hui;GU Kang-sheng(Department of Medical Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei 246001,Anhui Province,China)

机构地区：[1]安徽医科大学附属第一医院肿瘤内科,安徽合肥246001

出　　处：《中国临床药理学杂志》2022年第7期657-660,666,共5页The Chinese Journal of Clinical Pharmacology

基　　金：安徽省自然科学基金面上基金资助项目(1808085MH306)。

摘　　要：目的研究叉头框家族D3(FOXD3)和腺苷酸活化蛋白激酶5(ARK5)参与胃癌顺铂耐药的机制。方法将细胞株分为6组:SGC7901组(1组);SGC7901/DDP组(2组)、SGC7901/DDP-FOXD3组(3组)、SGC7901/DDP-FOXD3-NC组(4组)、SGC7901/DDP-shARK5组(5组)和SGC7901/DDP-shARK5-NC组(6组)。在第3组细胞株中转染过表达FOXD3质粒,第4组中转染FOXD3空白质粒作为对照,在第5组细胞株中转染敲降shARK5质粒,第6组细胞株转染敲降shARK5空白对照质粒。用Western blot法检测FOXD3和ARK5蛋白的表达水平,用噻唑蓝比色法测定顺铂半抑制浓度(IC;)。结果第1至6组中FOXD3蛋白相对表达量分别为27.15±7.53,22.04±3.92,45.39±5.17,23.39±2.56,21.99±4.74和24.27±5.39,ARK5蛋白相对表达量分别为25.33±5.11,27.56±3.45,27.82±5.40,27.21±5.22,10.33±0.82和28.44±1.63;第3组的FOXD3蛋白相对表达量均明显高于其他5组,差异均有统计学意义(均P<0.05);第5组的ARK5蛋白相对表达量均明显低于其他5组,差异均有统计学意义(均P<0.01)。第1至6组的IC;分别为(1.92±0.41),(3.54±1.10),(1.54±0.31),(4.23±1.22),(1.94±0.40)和(5.06±1.32)mg·mL^(-1)。第2组的IC;明显高于第1组,第3组的IC;明显低于第4组,第5组的IC;明显低于第6组,差异均有统计学意义(均P<0.01)。结论FOXD3表达升高可提高耐顺铂胃癌细胞对顺铂的敏感性,ARK5则促进耐顺铂胃癌细胞对顺铂的耐药性,二者的异常表达可能共同参与了胃癌的顺铂耐药机制。Objective To investigate the mechanism of forkhead box D3(FOXD3)and AMPK-related kinase 5(ARK5)involved in cisplatin resistance of gastric cancer.Methods The cell lines were divided into six groups:SGC7901 group(group 1),SGC7901/DDP group(group2),SGC7901/DDP-FOXD3 group(group 3),SGC7901/DDP-FOXD3-NC group(group 4),SGC7901/DDP-sh ARK5 group(group5)and SGC7901/DDP-sh ARK5-NC group(group 6).FOXD3overexpression plasmid was transfected into the cells of group 3,FOXD3blank plasmid was transfected into the cells of group 4 as control,sh ARK5 knockdown plasmid was transfected into the cells of group 5,sh ARK5 knockdown blank control plasmid was transfected into the cells of group 6.Western blot was used to detect the protein expression of FOXD3 and ARK5.The half inhibitory concentration(IC;)of cisplatin was determined by methyl thiazolyl tetrazolium assay,and the cell viability was observed.Results The expression levels of FOXD3 in the first group to sixth group were 27.15±7.53,22.04±3.92,45.39±5.17,23.39±2.56,21.99±4.74 and 24.27±5.39,the expression levels of ARK5 were 25.33±5.11,27.56±3.45,27.82±5.40,27.21±5.22,10.33±0.82 and 28.44±1.63.The expression of FOXD3 in group 3 was significantly higher than that in other 5 groups(all P<0.05);the expression of ARK5 in group 5 was significantly lower than that in other 5 groups(all P<0.01).The IC;of in the first group to sixth group were(1.92±0.41),(3.54±1.10),(1.54±0.31),(4.23±1.22),(1.94±0.40)and(5.06±1.32)mg·m L^(-1).The IC;of group 2 was significantly higher than that of group 1.The IC50 of group 3 was significantly lower than that of group 4;the IC;of group 5 was significantly lower than that of group 6(all P<0.01).Conclusion The increased expression of FOXD3 can improve the sensitivity of cisplatin resistant gastric cancer cells to cisplatin,while ARK5 can promote the resistance of cisplatin resistant gastric cancer cells to cisplatin.The abnormal expression of FOXD3 and ARK5 may be involved in the mechanism of cisplatin resistance of gastric cancer cel

关 键 词：胃癌 顺铂耐药 叉头框家族D3 腺苷酸活化蛋白激酶5 

分 类 号：R979.1[医药卫生—药品]