摘要
化学致癌过程是涉及启动、促进和进展等多阶段的复杂过程。癌症的化学预防是应用天然的或合成的化学物质,以阻断、抑制或其癌变过程,从而达到预防肿瘤的目的。化学致癌物的体内生物转化依靠肝脏的Ⅰ相和Ⅱ相代谢相酶来完成。作为对化学预防剂的应答反应,碱性亮氨酸拉链蛋白家族成员转录因子Nrf2首先从胞质蛋白Keap1上解离,然后发生核内转位,与Ⅱ相代谢酶基因上游的抗氧化反应元件结合诱导Ⅱ相代谢酶基因的表达,这是化学防癌的重要机制;Nrf2/ARE对Ⅱ相代谢酶的调节涉及PI3K、MAPK、PKC等细胞内重要信号传导途径。这些发现加深了化学防癌机制的认识并为评估潜在抗癌物质提供了新的策略。
Chemical carcinogenesis is involved in complicated multiple stages of initiation, promotion and progression. Chemoprevention comprises multiple intervention methods using either pharmacological or dietary agents to impede, arrest, or reverse carcinogenesis at various stages. Biotransformation of carcinogens may be associated with hepatic phase Ⅰ and Ⅱ detoxifying enzymes. It is proved that Nrf2, a member of the basic-leucine zipper family of transcription factors, is dissociated from cytoplasmic protein Keapl firstly in response to activation by chemopreventive agents, then translocated into nucleic, and binding with the antioxidant response element （ARE） to induce expression of phase Ⅱ enzyme gene, which plays a crucial role in protection against carcinogenesis. Regulation of Phase Ⅱ enzyme by Nrf2/ARE is also involved with PI3K, MAPK and PKC signal transduction pathways. Recent analyses argue that these pathways provide a insight into carcinogenesis and new strategies to evaluate vast potential chemopreventive agents.
出处
《中华肿瘤防治杂志》
CAS
2007年第3期222-225,共4页
Chinese Journal of Cancer Prevention and Treatment
