维生素C抗肿瘤机制  

The anti-tumor mechanism of vitamin C

作　　者：赵文芝 石汉平 ZHAO Wen-zhi;SHI Han-ping(Department of Gastrointestinal Surgery/Clinical Nutrition,Beijing Shijitan Hospital/Capital Medical University Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition/Department of Oncology,Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院胃肠外科/临床营养科/肿瘤代谢与营养北京市国际科技合作基地/首都医科大学肿瘤学系,北京100038

出　　处：《肿瘤代谢与营养电子杂志》2019年第4期409-414,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家重点研发计划项目(2017YFC1309200);北京市临床重点专科(肿瘤科)建设项目(2018ZLLCZDZK4)。

摘　　要：维生素C是具有重要生理作用的必需营养素,具有抗氧化、抗衰老、预防和治疗缺铁性贫血的作用,参与胶原、肉碱、儿茶酚胺类激素、酰胺化肽激素的合成,能够羟化转录因子。维生素C抗肿瘤研究已接近半个世纪,其抗肿瘤效果由肯定到否定、再到肯定,经历了质疑与验证的沉浮。维生素C的抗肿瘤机制目前主要有3种假说,即维生素C通过诱导的过氧化应激杀伤肿瘤细胞、通过调节表观遗传学改变及调节低氧诱导因子-1的活性改变肿瘤细胞的恶性程度,即兼具杀伤肿瘤细胞和增强肿瘤细胞对治疗敏感性的功能。维生素C诱导的过氧化应激反应过程中,由于产生过氧化氢或者由于脱氢抗坏血酸的氧化还原,导致细胞内部能量耗竭;维生素C调节表观遗传学改变过程中,通过增强具有脱甲基作用的酶的活性,降低DNA或组蛋白甲基化水平,从而降低肿瘤细胞的恶性程度;维生素C调节低氧诱导因子-1活性的过程中,通过增强细胞内低氧诱导因子羟化酶活性抑制低氧诱导因子-1转录反应,从而降低肿瘤细胞的恶性程度。关于其抗肿瘤的效果和应用前景目前仍存在争议,促使人们去探索关于其敏感性、用药剂量等问题。维生素C的抗肿瘤研究有望为肿瘤治疗提供新的思路。Vitamin C is an essential nutrient with important physiological function of anti-oxidant activity,anti-aging activity,preventing and treating iron deficiency anemia,being involved in synthesis of collagen,carnitine,catecholamines,and aminopeptide hormones,and biochemical reaction of hydroxylation of transcription factors.It has been nearly half a century since the beginning of researches of anti-tumor effect of vitamin C and the effect was challenged and verified repeatedly.At present,there are three main hypotheses about the anti-tumor mechanism of vitamin C,that is targeting redox imbalance to kill tumor cells,or targeting epigenetic regulators or targeting hypoxia-inducible factor 1(HIF-1)signaling to reduce the malignancy and enhance the sensitivity to treatment of cancer cells.In the mechanism of targeting redox imbalance,intracellular energy is exhausted due to the generation of H2O2 or the oxidation and reduction of the dehydroascorbic acid.In the mechanism of targeting epigenetic regulators,malignancy of the tumor cells is reducing through demethylation of DNA or histone catalyzed by enhancing activity of the related enzyme.In the mechanism of targeting HIF-1,malignancy of the tumor cells is reducing through inhibiting transcription of HIF-1 by enhancing activity of HIF hydroxylase.It\s controversial about the efficiency and the prospect of vitamin C in treatment of cancer,which has led to the exploration of the question of drug sensitivity and dosage.Research on the anti-tumor effect of vitamin C is expected to provide a new way for the treatment of cancer.

关 键 词：维生素C 过氧化应激 脱甲基 缺氧诱导因子 

分 类 号：R730.5[医药卫生—肿瘤]