Sahin Kazim, Orhan Cemal, Tuzcu Mehmet, Sahin Nurhan, Ali Shakir, Bahcecioglu Ibrahim H, Guler Osman, Ozercan Ibrahim, Ilhan Necip, Kucuk Omer
a Department of Animal Nutrition, Faculty of Veterinary Science , Firat University , Elazig , Turkey.
Nutr Cancer. 2014;66(4):590-8. doi: 10.1080/01635581.2014.894092. Epub 2014 Mar 24.
Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an intraperitoneal injection of DEN followed by promotion with phenobarbital for 24 successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week orally for 4 wk prior to initiation, and the treatment was continued for 24 consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin, and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione decreased in DEN-treated rats when compared with the control group. Lycopene significantly reversed these biochemical changes and increased the expression of NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF-κB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating antioxidant signaling (P < 0.05). Lycopene also decreased DEN-induced increases in phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein kinase B (P < 0.05). Lycopene is an active chemopreventive agent that offers protection against DEN-induced hepatocarcinogenesis by inhibiting NF-κB and mTOR pathways.
肝癌发生是最常见且致命的癌症之一。我们研究了番茄红素抑制大鼠二乙基亚硝胺（DEN）诱导的肝癌发生的潜在机制。通过腹腔注射DEN诱导肝癌发生，随后用苯巴比妥连续促进24周。在开始诱导前，大鼠每周口服3次番茄红素（20毫克/千克体重），持续4周，并持续治疗24周。番茄红素降低了肝结节的发生率、数量、大小和体积。与对照组相比，DEN处理的大鼠血清丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素和丙二醛（MDA）显著升高，肝脏抗氧化酶（过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶）和谷胱甘肽降低。番茄红素显著逆转了这些生化变化，增加了NF-E-2相关因子2/血红素加氧酶-1的表达，并降低了NF-κB/环氧化酶-2，抑制了炎症级联反应并激活了抗氧化信号通路（P<0.05）。番茄红素还降低了DEN诱导的磷酸化雷帕霉素哺乳动物靶标（p-mTOR）、磷酸化p70核糖体蛋白S6激酶1、磷酸化4E结合蛋白1和蛋白激酶B的增加（P<0.05）。番茄红素是一种活性化学预防剂，通过抑制NF-κB和mTOR途径对DEN诱导的肝癌发生提供保护。
