中华临床医师杂志（电子版）
中華臨床醫師雜誌（電子版）
중화림상의사잡지（전자판）
CHINESE JOURNAL OF CLINICIANS(ELECTRONIC VERSION)
2014年
19期
3520-3524
,共5页
郑文键%张协军%黄国栋
鄭文鍵%張協軍%黃國棟
정문건%장협군%황국동
氧化性应激%抗药性,肿瘤%肿瘤,实验性%肿瘤标记,生物学%NF-E2相关因子2
氧化性應激%抗藥性,腫瘤%腫瘤,實驗性%腫瘤標記,生物學%NF-E2相關因子2
양화성응격%항약성,종류%종류,실험성%종류표기,생물학%NF-E2상관인자2
Oxidative stress%Drug resistance,antineoplastic%Experimental neoplasm%Tumor markers,biological%Nuclear factor-E2-related factor 2
活性氧自由基（ROS）可以损伤细胞DNA和蛋白质，具有致癌作用。Nrf2可以激活人体内多种Ⅱ相解毒酶的表达，其活性主要由Keap1负性调节，当机体受到外界药物、射线等刺激时， Nrf2可激活ARE区域，介导氧化应激反应，起到保护细胞的作用，目前已有部分研究表明某些植物与药物通过Nrf2信号通路发挥抗癌作用。近期，大量的细胞及动物实验表明Nrf2同样具有致癌作用，肿瘤细胞通过Nrf2或Keap1突变与基因杂合性丢失，使Nrf2和Keap1不能正常结合，导致Nrf2在胞内积累，激活下游基因，增加肿瘤细胞内的解毒酶，从而增强细胞对放化疗的抵抗性。同时，研究发现Nrf2在人体的大部分消化系统、呼吸系统、生殖系统及神经系统肿瘤中均呈高表达，并与多种致癌基因如Ki67、K-Ras、B-Raf、Myc、BRCA1等基因表达相关，阻断Nrf2信号通路的抗癌药物研究已表明其能够减少肿瘤复发率并增加肿瘤对放化疗药物的敏感性。Nrf2参与着各个系统众多肿瘤的发生与发展，将成为未来肿瘤靶向治疗的重点目标。
活性氧自由基（ROS）可以損傷細胞DNA和蛋白質，具有緻癌作用。Nrf2可以激活人體內多種Ⅱ相解毒酶的錶達，其活性主要由Keap1負性調節，噹機體受到外界藥物、射線等刺激時， Nrf2可激活ARE區域，介導氧化應激反應，起到保護細胞的作用，目前已有部分研究錶明某些植物與藥物通過Nrf2信號通路髮揮抗癌作用。近期，大量的細胞及動物實驗錶明Nrf2同樣具有緻癌作用，腫瘤細胞通過Nrf2或Keap1突變與基因雜閤性丟失，使Nrf2和Keap1不能正常結閤，導緻Nrf2在胞內積纍，激活下遊基因，增加腫瘤細胞內的解毒酶，從而增彊細胞對放化療的牴抗性。同時，研究髮現Nrf2在人體的大部分消化繫統、呼吸繫統、生殖繫統及神經繫統腫瘤中均呈高錶達，併與多種緻癌基因如Ki67、K-Ras、B-Raf、Myc、BRCA1等基因錶達相關，阻斷Nrf2信號通路的抗癌藥物研究已錶明其能夠減少腫瘤複髮率併增加腫瘤對放化療藥物的敏感性。Nrf2參與著各箇繫統衆多腫瘤的髮生與髮展，將成為未來腫瘤靶嚮治療的重點目標。
활성양자유기（ROS）가이손상세포DNA화단백질，구유치암작용。Nrf2가이격활인체내다충Ⅱ상해독매적표체，기활성주요유Keap1부성조절，당궤체수도외계약물、사선등자격시， Nrf2가격활ARE구역，개도양화응격반응，기도보호세포적작용，목전이유부분연구표명모사식물여약물통과Nrf2신호통로발휘항암작용。근기，대량적세포급동물실험표명Nrf2동양구유치암작용，종류세포통과Nrf2혹Keap1돌변여기인잡합성주실，사Nrf2화Keap1불능정상결합，도치Nrf2재포내적루，격활하유기인，증가종류세포내적해독매，종이증강세포대방화료적저항성。동시，연구발현Nrf2재인체적대부분소화계통、호흡계통、생식계통급신경계통종류중균정고표체，병여다충치암기인여Ki67、K-Ras、B-Raf、Myc、BRCA1등기인표체상관，조단Nrf2신호통로적항암약물연구이표명기능구감소종류복발솔병증가종류대방화료약물적민감성。Nrf2삼여착각개계통음다종류적발생여발전，장성위미래종류파향치료적중점목표。
Reactive oxygen species (ROS) were known to be detrimental to DNA and protein and can potentially promote carcinogenesis. The transcription factor nuclear factor (erythroid-derived 2)-like 2, also known as Nrf2, is a master regulator of the anti-oxidative stress response and regulate the expression of a battery of phase Ⅱ detoxifying enzyme responding to oxidative stress evoked by xenobiotics or radiation. Epidemiological evidence has suggested that consumption of certain plants can reduce the risk of several types of cancer through activation of Nrf2 pathway. Recently, large numbers of cell researches and animal experiments have revealed the pro-tumorigenic effect of Nrf2 in elevating the level of detoxifying enzyme in tumor cells, which enhance their resistance to chemotherapy or radiation. Studies also reported that Nrf2 was highly expressed in various human tumors of digestive system, respiratory system, reproductive system and nervous system. Nrf2 pathway can also induce over-expression of certain oncogenes such as Ki67, K-Ras, B-Raf, Myc and BRCA1 in specific cancer type and further promote cancer development. Compounds targeted on Nrf2 pathway have been showen to decrease tumor recurrence rate and increase chemo-and radio-sensitivity. Therapeutic strategies targeting Nrf2 may attend better results on “Nrf2-dominant” cancer types, indicating that Nrf2 is a potential therapeutic target on cancers in different body systems.
