铜与氧化应激水平升高在肿瘤恶性进展中居重要地位。肝脏是铜代谢的主要器官，铜与肝癌关系有待进一步阐明。金属调节转录因子-1(MTF-1)在维持金属稳态中起关键作用。前期发现铜诱导细胞增殖并伴MTF-1表达增强，敲减MTF-1后肝癌细胞增殖及侵袭能力减弱。APE/Ref-1（脱嘌呤/脱嘧啶核苷酸内切酶/氧化还原效应因子1）是细胞对氧化应激重要的反应调控因子。前期发现铜激活APE/Ref-1并参与肝癌发生发展，而且APE/Ref-1与MTF-1特异性结合。综上，我们推测MTF-1与APE/Ref-1可相互作用并调控下游靶基因促进肝癌恶性进展。本研究拟评估MTF-1/APE/Ref-1临床诊断价值以及靶向治疗的临床意义，阐明MTF-1对肝癌细胞增殖、失巢凋亡、侵袭转移的调控作用，探讨MTF-1与APE/Ref-1相互作用内在分子机制以及参与调控肿瘤发生发展功能，为发现新的治疗靶点提供理论基础。

Accumulating evidences have demonstrated that elevated copper levels and oxide stress in a variety of malignancies have been shown to be directly correlated to cancer progression. Particularly, liver is the primary organ in the supply, storage and excretion of copper, underlying role of copper involved in Hepatocellular carcinoma (HCC) has not been well defined. Metal-regulatory transcription factor-1 (MTF-1) plays an important role in maintaining metal homeostasis. Previous study done in our group showed that copper effectively stimulated proliferation in hepatocellular carcinoma with increased MTF-1 expression levels both in HCC cell lines and in tumor tissues versus matched adjacent non-tumor tissues. Knockdown of MTF-1 using siRNA significantly reduced the proliferation and invasion potential of HCC cells, however, the molecular mechanisms need to be investigated. Apurinic apyrimidinic endonuclease/redox effector factor 1 (APE/Ref-1) is a multifunctional enzyme that is involved in DNA repair and regulates transcription factors in a redox-dependent manner. APE/Ref-1 was shown playing an important role in HCC progression and our Co-IP study showed specific binding between APE/Ref-1 and MTF-1, indicating an important role of APE/Ref-1 in regulating MTF-1 expression after copper treatment. Taken together, we hypothesized that MTF-1 and APE/Ref-1 may facilitate tumorigenesis and progression by acting on the target genes in HCC, which provides for a prospect of selective HCC targeted treatment in the future.