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目的:探讨抗白细胞介素-6(IL-6)单克隆抗体司妥昔单抗(siltuximab)对IL-6介导的基因表达的影响。方法:采用Affymetrix人类基因组表达谱芯片U133 Plus 2.0,检测经IL-6处理的卵巢癌细胞株SKOV-3(SKOV-3+IL-6)和Caov-3(Caov-3+IL-6)中相关基因的表达水平。通过Taq Man实时定量PCR分析,研究siltuximab对卵巢癌细胞株(SKOV-3、Caov-3)中IL-6介导的基因表达的影响。结果:1经Affymetrix人类基因组测定:经IL-6处理后,SKOV-3+IL-6和Caov-3+IL-6细胞株中分别有506个和674个基因上调,其中27个基因在两种细胞株中均表现出10倍上调。2经siltuximab处理后,在SKOV-3+IL-6+siltuximab和Caov-3+IL-6+siltuximab细胞株中,分别有634个和679个基因出现10倍降调,还有31个基因在两种细胞中均表现出10倍降调。3对在两种细胞株中经IL-6处理后均过度表达的多肽三烯B4(UGT2B4)和ATP细胞膜钙转运2(ATP2B2)基因经siltuximab处理后,Taq Man实时定量PCR示,SKOV-3+IL-6+siltuximab和Caov-3+IL-6+siltuximab细胞株中UGT2B4基因的表达分别降调3倍和17倍,ATP2B2基因的表达分别降调10倍和7倍。结论:IL-6在卵巢癌发生发展中发挥着一定作用,是治疗卵巢癌的一个重要的靶点。siltuximab可以有效地阻断IL-6介导的UGT2B4和ATP2B2基因在这些细胞中的表达,可能为卵巢癌的基因治疗提供新思路。
Objective: To investigate the effect of anti-interleukin-6 (IL-6) monoclonal antibody siltuximab on IL-6-mediated gene expression. Methods: Human ovarian cancer cell line SKOV-3 (SKOV-3 + IL-6) and Caov-3 + IL-6 were treated with Affymetrix Human Genome Profiling U133 Plus 2.0. Related gene expression levels. The effect of siltuximab on IL-6-mediated gene expression in ovarian cancer cell lines (SKOV-3, Caov-3) was investigated by real-time TaqMan quantitative PCR analysis. Results: 1 Affymetrix human genome assay: After IL-6 treatment, 506 and 674 genes were upregulated in SKOV-3 + IL-6 and Caov-3 + IL-6 cell lines, respectively. Cell lines showed a 10-fold increase. 2 After siltuximab treatment, 634 and 679 genes were down-regulated by 10 times in SKOV-3 + IL-6 + siltuximab and Caov-3 + IL-6 + siltuximab cell lines, respectively, Both cells showed a 10-fold down-regulation. 3 After siltuximab treatment of the polypeptides triluen B4 (UGT2B4) and ATP2B2 (overexpressed) in both cell lines after IL-6 treatment, Taq Man real-time quantitative PCR showed that SKOV-3 + IL-6 + siltuximab and Caov-3 + IL-6 + siltuximab cell lines were down-regulated by 3-fold and 17-fold, respectively, and the expression of ATP2B2 gene was reduced by 10-fold and 7-fold, respectively. Conclusion: IL-6 plays a role in the development of ovarian cancer and is an important target for the treatment of ovarian cancer. siltuximab can effectively block the expression of IL-6-mediated UGT2B4 and ATP2B2 genes in these cells, which may provide new ideas for the gene therapy of ovarian cancer.