锌转运体8对结肠癌奥沙利铂耐药的影响

Effect of zinc transporter 8 on oxaliplatin resistance in colon cancer

目的:筛选结肠癌中奥沙利铂耐药相关基因,并验证其对奥沙利铂治疗结肠癌疗效的影响。方法:从NCBI⁃GEO数据库下载并综合分析数据集GSE42387,筛选奥沙利铂耐药相关基因;通过Ualcan和GEPIA数据库检测耐药相关基因在结肠癌中的表达和对预后的影响;转染siRNA⁃ZIP8干扰结肠癌细胞SW620中锌转运体8(zinc transporter 8,ZIP8)表达;CCK⁃8实验检测ZIP8表达降低后奥沙利铂对结肠癌细胞增殖抑制的影响;流式细胞术检测ZIP8表达降低后奥沙利铂对结肠癌细胞凋亡的影响;对化疗前结肠癌组织标本进行免疫组织化学染色,评估ZIP8与化疗效果的关系。结果:筛选出ZIP8、NUPR1、SLC43A1和TEME73共4个耐药相关基因;ZIP8在结肠癌组织中高表达(P<0.05),且与患者预后相关(P=0.005);在相同药物浓度下,siZIP8组细胞的增殖抑制率明显高于siNC组(P<0.05),siZIP8组中奥沙利铂诱导的细胞凋亡率显著高于siNC组(P<0.05);ZIP8低表达的患者有更长的总生存期(P=0.001)和无病生存期(P<0.001)。结论:ZIP8促进了结肠癌患者的奥沙利铂耐药性,可作为预测患者化疗预后的指标之一。

Objective:To screen genes related to oxaliplatin resistance in colon cancer and verify the influence of them on the oxaliplatin treatment of colon cancer.Methods:Data set GSE42387 was downloaded from NCBI⁃GEO and analyzed comprehensively,and oxaliplatin resistance genes were screened.Ualcan and GEPIA databases were used to detect the expression of drug⁃resistant genes in colon cancer and their influence on prognosis.Transfection of siRNA⁃ZIP8 interfered with zinc transporter 8(ZIP8)expression in colon cancer cell SW620.CCK⁃8 proliferation assay detected the effect of oxaliplatin on colon cancer cell proliferation inhibition after ZIP8 expression was inhibited.Flow cytometry was used to detect the effect of oxaliplatin on colon cancer cell apoptosis after the expression of ZIP8 was decreased.Immunohistochemical staining was performed on colon cancer tissue samples before chemotherapy to evaluate the relationship between ZIP8 and chemotherapy effect.Results:Four drug⁃resistant genes(ZIP8,NUPR1,SLC43A1 and TEME73)were selected.ZIP8 was highly expressed in colon cancer tissues(P<0.05)and correlated with patient prognosis(P=0.005).Under the same drug concentration,the proliferation inhibition rate of the siZIP8 group was significantly lower than that in the siNC group,the half inhibitory concentration of oxaliplatin in the siZIP8 group was lower than that in the siNC group(P<0.05).Patients with low ZIP8 expression had longer overall survival(P=0.001)and disease⁃free survival(P<0.001).Conclusion:ZIP8 promotes oxaliplatin resistance in colon cancer patients and can be used as an indicator for the prognosis of chemotherapy.