Yokomatsu H, Hiura A, Tsutsumi M, Satake K
First Department of Surgery, Osaka City University Medical School, Japan.
Pancreas. 1996 Aug;13(2):154-9. doi: 10.1097/00006676-199608000-00006.
Sarcophytol A (SaA), a cembrane-type diterpene, inhibits pancreatic carcinogenesis induced by N-nitrosobis(2-oxypropyl)amine (BOP) in hamsters. The experimental groups received two injections of BOP at 70 mg/kg dose, followed 2 weeks later by a 20 mg/kg dose injection, and were fed a basal diet or 0.01 and 0.05% SaA diets starting 1 week after the second injection of BOP. Control groups were injected with normal saline and fed the basal diet or the 0.05% SaA diet. All animals were killed 30 weeks after the start of the experiments. Seventeen BOP-treated hamsters fed the basal diet developed pancreatic tumors (77.3%) while only 12 of 21 hamsters fed the 0.01% SaA diet (57.1%) and 12 of 23 hamsters fed the 0.05% SaA diet (52.2%) developed pancreatic tumors. Pancreatic lesions included ductal hyperplasia, atypical ductal hyperplasia, and carcinoma in situ. Microscopic invasive carcinoma induced by BOP and the incidence of larger pancreatic tumors in hamsters were significantly higher in hamsters fed the basal diet than in hamsters fed the SaA diet (p < 0.05). The proliferating cell nuclear antigen (PCNA) labeling index of pancreatic carcinoma in BOP-treated hamsters fed the basal diet was 41.2 +/- 13.4%, whereas BOP-treated hamsters fed 0.01 and 0.05% SaA diets yielded PCNA indexes of 26.8 +/- 8.3 and 28.4 +/- 7.0%, respectively. k-ras mutation was detected in 40% of cancers in both groups. No pancreatic tumors developed in saline-treated groups, and no differences in body weights or histological findings in their organs, including the pancreas, were observed in either group. These findings suggest that SaA not only inhibits BOP-induced pancreatic carcinogenesis in hamsters, but also provides antipromotion and antiprogression effects on these tumors, even when SaA commences 1 week after the initiation of pancreatic carcinogenesis.
肉珊瑚醇A（SaA）是一种西松烷型二萜，可抑制N-亚硝基双（2-氧丙基）胺（BOP）诱导的仓鼠胰腺癌发生。实验组接受两次剂量为70mg/kg的BOP注射，2周后再注射一次剂量为20mg/kg的BOP，在第二次注射BOP后1周开始，分别给予基础饮食或含0.01%和0.05% SaA的饮食。对照组注射生理盐水并给予基础饮食或含0.05% SaA的饮食。实验开始30周后处死所有动物。17只接受BOP处理并喂食基础饮食的仓鼠发生了胰腺肿瘤（77.3%），而在21只喂食含0.01% SaA饮食的仓鼠中只有12只（57.1%）发生了胰腺肿瘤，在23只喂食含0.05% SaA饮食的仓鼠中有12只（52.2%）发生了胰腺肿瘤。胰腺病变包括导管增生、非典型导管增生和原位癌。喂食基础饮食的仓鼠中，BOP诱导的显微镜下浸润性癌和较大胰腺肿瘤的发生率显著高于喂食含SaA饮食的仓鼠（p < 0.05）。喂食基础饮食的BOP处理仓鼠胰腺癌的增殖细胞核抗原（PCNA）标记指数为41.2±13.4%，而喂食含0.01%和0.05% SaA饮食的BOP处理仓鼠的PCNA指数分别为26.8±8.3%和28.4±7.0%。两组中40%的癌症检测到k-ras突变。生理盐水处理组未发生胰腺肿瘤，两组在体重或包括胰腺在内的器官组织学检查结果上均未观察到差异。这些发现表明SaA不仅能抑制仓鼠中BOP诱导的胰腺癌发生，而且即使在胰腺癌发生起始1周后开始给予SaA，它对这些肿瘤也具有抗促癌和抗进展作用。
