摘要目的 肝细胞癌(HCC)是世界范围内最常见的恶性肿瘤之一.转移是肝癌患者恶化的标志和死亡的主要原因.为了制定有效的治疗策略,迫切需要研究肝癌转移的分子基础. 方法 免疫组织化学检测脂肪酸合成酶(FASN)在肝癌中的表达.划痕试验和细胞侵袭试验验证FASN在肝癌迁移和侵袭中的作用.采用ITRAQ(同位素标记的相对与绝对定量)鉴定与FASN相互作用的蛋白质.免疫共沉淀(Co-IP)和细胞免疫荧光分析用于评估FASN和信号传导及转录激活因子3 (STAT3)之间的相互作用.采用蛋白质印迹法检测FASN敲低后STAT3、P-STAT3、基质金属蛋白酶(MMP)-2和MMP-9的表达.采用t检验进行统计学分析.结果 免疫组织化学检测结果显示FASN在肝癌组织中的表达高于癌旁组织.ITRAQ、Co-IP和免疫荧光分析发现FASN与STAT3存在相互作用.蛋白质印迹法检测结果表明FASN敲低后,P-STAT3、MMP-2和MMP-9的表达降低. 结论 FASN可能通过与STAT3相互作用和影响MMP-2/MMP-9的表达从而促进肝癌的转移.

abstractsObjective Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide.Metastasis is a marker of cancer deterioration in patients with liver cancer and a major cause of death.In order to develop effective therapeutic strategies,it is urgent to study the molecular basis of liver cancer metastasis.Methods Immunohistochemistry was used to detect the expression of fatty acid synthase (FASN) in HCC.Wound healing and transwell cell invasion assays was used to confirm the role of FASN in liver cancer migration and invasion.Proteins that interacted with FASN were identified using iTRAQ (isobaric tag for relative and absolute quantification).Co-immunoprecipitation (Co-IP) and cellular immunofluorescence analysis were used to assess the interaction between FASN and signal transduction and transcription activator 3 (STAT3).The expression of STAT3,p-STAT3,matrix metalloproteinase (MMP)-2 and MMP-9 was detected after FASN knockdown using Western blot method.Statistical analysis was performed using the t-test.Results Immunohistochemistry showed that the expression of FASN in HCC tissue was higher than that in adjacent tissues.iTRAQ,Co-IP and immunofluorescence analysis revealed that FASN interacted with STAT3.Western blot analysis showed that the expression of p-STAT3,MMP-2 and MMP-9 decreased after FASN knockdown.Conclusion FASN may promote the metastasis of liver cancer by interacting with STAT3 and affecting the expression of MMP-2/MMP-9.