Furihata Tadashi, Kawamata Hitoshi, Kubota Keiichi, Fujimori Takahiro
Department of Gastroenterological Surgery, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
Int J Mol Med. 2002 Apr;9(4):353-8.
We previously showed that colitis enhanced the development of cancer and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in Fischer 344 rats. In this study, we examined the effect of two different anti-inflammatory drugs [non-steroidal anti-inflammatory drugs (NSAIDs: Fenbufen) and a platelet activating factor-receptor antagonist (PAF-RA)] on the inflammation-induced rat colon carcinogenesis. Furthermore, we examined the expression and the localization of beta-catenin protein, and the proliferating cell nuclear antigen (PCNA)-labeling index (LI) in ACF and cancer. PAF-RA significantly decreased the incidence of ACF in the rats (p<0.05), but Fenbufen did not affect the incidence of ACF and cancer. In most of the ACF (91%), beta-catenin was localized at the cell membrane like in normal colon epithelium. In about 9% of the ACF, beta-catenin was overexpressed not only on the cell membrane but also in the cytoplasm. In all of the cancer cells, beta-catenin was overexpressed in the nucleus. When we compared the PCNA-LI in the ACF showing normal beta-catenin expression pattern with that in the ACF showing abnormal beta-catenin expression pattern (overexpression in cytoplasm), there was no significant difference of the PCNA-LI in these two different types of ACF. These findings suggest that immunohistochemical staining of ACF for beta-catenin can evaluate the malignant potential of ACF, and that PAF-RA can be used for preventing the development of ACF in inflammation-induced carcinogenesis.
我们之前的研究表明,在费希尔344大鼠中,结肠炎会增强1,2 - 二甲基肼(DMH)诱导的结肠癌发生及异常隐窝病灶(ACF)的发展。在本研究中,我们检测了两种不同抗炎药物[非甾体抗炎药(NSAIDs:芬布芬)和血小板活化因子受体拮抗剂(PAF - RA)]对炎症诱导的大鼠结肠癌发生的影响。此外,我们检测了β - 连环蛋白的表达及定位,以及ACF和癌组织中增殖细胞核抗原(PCNA)标记指数(LI)。PAF - RA显著降低了大鼠ACF的发生率(p<0.05),但芬布芬对ACF和癌的发生率没有影响。在大多数ACF(91%)中,β - 连环蛋白像在正常结肠上皮中一样定位于细胞膜。在约9%的ACF中,β - 连环蛋白不仅在细胞膜上过度表达,还在细胞质中过度表达。在所有癌细胞中,β - 连环蛋白在细胞核中过度表达。当我们比较β - 连环蛋白表达模式正常的ACF与β - 连环蛋白表达模式异常(细胞质中过度表达)的ACF中的PCNA - LI时,这两种不同类型的ACF中的PCNA - LI没有显著差异。这些发现表明,对ACF进行β - 连环蛋白的免疫组化染色可以评估ACF的恶性潜能,并且PAF - RA可用于预防炎症诱导的癌变中ACF的发展。