Central Animal Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Semin Immunopathol. 2013 Mar;35(2):203-27. doi: 10.1007/s00281-012-0340-x. Epub 2012 Sep 7.
Chronic inflammation is known to be a risk for many cancers, including pancreatic cancer. Heavy alcohol drinking and cigarette smoking are major causes of pancreatitis, and epidemiological studies have shown that smoking and chronic pancreatitis are risk factors for pancreatic cancer. Meanwhile, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are elevated in pancreatitis and pancreatic cancer tissues in humans and in animal models. Selective inhibitors of iNOS and COX-2 suppress pancreatic cancer development in a chemical carcinogenesis model of hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). In addition, hyperlipidemia, obesity, and type II diabetes are also suggested to be associated with chronic inflammation in the pancreas and involved in pancreatic cancer development. We have shown that a high-fat diet increased pancreatic cancer development in BOP-treated hamsters, along with aggravation of hyperlipidemia, severe fatty infiltration, and increased expression of adipokines and inflammatory factors in the pancreas. Of note, fatty pancreas has been observed in obese and/or diabetic cases in humans. Preventive effects of anti-hyperlipidemic/anti-diabetic agents on pancreatic cancer have also been shown in humans and animals. Taking this evidence into consideration, modulation of inflammatory factors by anti-inflammatory agents will provide useful data for prevention of pancreatic cancer.
慢性炎症被认为是许多癌症的风险因素，包括胰腺癌。大量饮酒和吸烟是胰腺炎的主要原因，流行病学研究表明，吸烟和慢性胰腺炎是胰腺癌的危险因素。同时，诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）在人类和动物模型的胰腺炎和胰腺癌组织中升高。在 N-亚硝双（2-氧丙基）胺（BOP）处理的仓鼠化学致癌模型中，iNOS 和 COX-2 的选择性抑制剂可抑制胰腺癌的发展。此外，高脂血症、肥胖和 2 型糖尿病也被认为与胰腺的慢性炎症有关，并参与胰腺癌的发生。我们已经表明，高脂肪饮食会增加 BOP 处理的仓鼠的胰腺癌发展，同时伴有血脂异常加重、严重脂肪浸润以及胰腺中脂肪因子和炎症因子表达增加。值得注意的是，在肥胖和/或糖尿病患者的胰腺中也观察到了脂肪胰腺。降脂/降糖药物对胰腺癌的预防作用也在人类和动物中得到了证实。考虑到这些证据，抗炎药物对炎症因子的调节将为预防胰腺癌提供有用的数据。
