Chinery R, Brockman J A, Peeler M O, Shyr Y, Beauchamp R D, Coffey R J
Department of Cell Biology, Vanderbilt University Medical Center, and Veterans Affairs Medical Center, Nashville, Tennessee 37232, USA.
Nat Med. 1997 Nov;3(11):1233-41. doi: 10.1038/nm1197-1233.
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Five-fluorouracil (5FU) remains the single most effective treatment for advanced disease, despite a response rate of only 20%. Herein, we show that the antioxidants pyrrolidinedithiocarbamate and vitamin E induce apoptosis in CRC cells. This effect is mediated by induction of p21WAF1/CIP1, a powerful inhibitor of the cell cycle, through a mechanism involving C/EBPbeta (a member of the CCAAT/enhancer binding protein family of transcription factors), independent of p53. Antioxidants significantly enhance CRC tumor growth inhibition by cytotoxic chemotherapy in vitro (5FU and doxorubicin) and in vivo (5FU). Thus, chemotherapeutic agents administered in the presence of antioxidants may provide a novel therapy for colorectal cancer.
结直肠癌（CRC）是美国癌症死亡的第二大主要原因。尽管有效率仅为20%，但5-氟尿嘧啶（5FU）仍然是晚期疾病最有效的单一治疗方法。在此，我们表明抗氧化剂吡咯烷二硫代氨基甲酸盐和维生素E可诱导CRC细胞凋亡。这种效应是通过诱导p21WAF1/CIP1介导的，p21WAF1/CIP1是一种强大的细胞周期抑制剂，其机制涉及C/EBPβ（CCAAT/增强子结合蛋白转录因子家族的成员），独立于p53。抗氧化剂在体外（5FU和阿霉素）和体内（5FU）均显著增强细胞毒性化疗对CRC肿瘤生长的抑制作用。因此，在抗氧化剂存在下给予化疗药物可能为结直肠癌提供一种新的治疗方法。
