Herrington M K, Permert J, Kazakoff K R, Pour P M, Zuker K A, Bilchik A J, Adrian T E
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE.
Carcinogenesis. 1993 May;14(5):1021-6. doi: 10.1093/carcin/14.5.1021.
The mechanism by which high-fat diet potentiates pancreatic cancer is not known, but trophic hormones may be involved. In preliminary growth studies, hamsters fed a high fat diet (17.5% lard, 17.5% corn oil) for 14 days showed a 16.3% increase (P < 0.01) in pancreatic weight compared to controls on low fat diet (2.5% lard, 2.5% corn oil). A significant increase was also seen at 28 days. Similar increases were seen in pancreatic DNA (29%, P < 0.01) and pancreatic RNA (22%, P < 0.05) at 14 days. Plasma cholecystokinin (CCK) levels at 14 days were 2.5 fold higher in the animals fed high fat (P < 0.01). Infusion of the CCK antagonist MK329 (25 nmol/kg/h) completely abolished the increase in pancreatic weight, pancreatic DNA and pancreatic RNA. The effect of CCK receptor blockade during the initiation period of carcinogenesis was investigated in hamsters fed the same diets used in the growth studies. One hundred animals received a single injection of N-nitrosobis(2-oxopropyl)amine, (BOP, 20 mg/kg). Half of the hamsters in each diet group received a 2 week infusion of MK329 (25 nmol/kg/h), beginning 8 days before carcinogen administration. At the time of death, 55 weeks after carcinogen administration, non-fasting plasma CCK levels were 31% higher in the high fat fed hamsters than in the low fat fed animals (P < 0.01). The high-fat diet group had a 3-fold increase in total cancer incidence and a 5-fold increase in advanced lesions (adenocarcinomas). Tumor incidence and yield were not changed in either diet group by CCK-receptor blockade during the initiation period. Cholecystokinin appears to mediate the short-term trophic effect that high-fat feeding has on the pancreas. However, potentiation of pancreatic cancer by high-fat diet in the hamster cancer model does not appear to be influenced by endogenous cholecystokinin at the time of tumor induction.
高脂饮食增强胰腺癌的机制尚不清楚，但可能涉及营养激素。在初步的生长研究中，与低脂饮食（2.5%猪油、2.5%玉米油）的对照组相比，喂食高脂饮食（17.5%猪油、17.5%玉米油）14天的仓鼠胰腺重量增加了16.3%（P<0.01）。在28天时也观察到显著增加。在14天时，胰腺DNA（29%，P<0.01）和胰腺RNA（22%，P<0.05）也有类似增加。喂食高脂饮食的动物在14天时血浆胆囊收缩素（CCK）水平高出2.5倍（P<0.01）。输注CCK拮抗剂MK329（25nmol/kg/h）完全消除了胰腺重量、胰腺DNA和胰腺RNA的增加。在致癌作用起始期阻断CCK受体的作用，在喂食与生长研究相同饮食的仓鼠中进行了研究。100只动物单次注射N-亚硝基双（2-氧代丙基）胺（BOP，20mg/kg）。每个饮食组的一半仓鼠在致癌物给药前8天开始接受为期2周的MK329输注（25nmol/kg/h）。在致癌物给药55周后的死亡时，非空腹血浆CCK水平在高脂喂养的仓鼠中比低脂喂养的动物高31%（P<0.01）。高脂饮食组的总癌症发病率增加了3倍, 晚期病变（腺癌）增加了5倍。在起始期阻断CCK受体对两个饮食组的肿瘤发病率和产量均无影响。胆囊收缩素似乎介导了高脂喂养对胰腺的短期营养作用。然而，在仓鼠癌症模型中，高脂饮食对胰腺癌的增强作用在肿瘤诱导时似乎不受内源性胆囊收缩素的影响。
