Ikeda Ikuko, Tomimoto Ayako, Wada Koichiro, Fujisawa Toshio, Fujita Koji, Yonemitsu Kyoko, Nozaki Yuichi, Endo Hiroki, Takahashi Hirokazu, Yoneda Masato, Inamori Masahiko, Kubota Kensuke, Saito Satoru, Nagashima Yoji, Nakagama Hitoshi, Nakajima Atsushi
Gastroenterology Division, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Clin Cancer Res. 2007 Nov 1;13(21):6527-31. doi: 10.1158/1078-0432.CCR-07-1208.
The risk of colorectal cancer is increased in patients with inflammatory bowel diseases, especially those with ulcerative colitis (UC). Although 5-aminosalicylic acid (5-ASA) is widely used in the treatment of UC to suppress the colitic inflammation, no studies have been conducted to examine the chemopreventive effect of 5-ASA, given in the remission phase of colitis, against colitis-associated cancer using animal models. We therefore investigated the possible inhibition by peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model.
A dextran sodium sulfate/azoxymethane-induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPARgamma ligands, given in the remission phase of colitis, against colitis-related colon carcinogenesis, were evaluated.
The number of neoplasms in the mice treated with 5-ASA was significantly lower than that in the control mice. In addition, the size of the neoplasms in treated mice was also significantly smaller than that in the control mice. In contrast, no significant suppression in the number or size of the tumors was observed in the mice treated with PPARgamma ligands. The proliferating cell nuclear antigen-labeling index in the tumor cells of the 5-ASA-treated mice was significantly smaller than that in the control, indicating that 5-ASA reduced tumor cell proliferation.
Our results revealed that 5-ASA given in the remission phase of colitis significantly suppressed the development of colitis-associated cancer in a mouse model, which indicates the clinical importance of adopting chemopreventive strategies even in UC patients in remission.
炎症性肠病患者,尤其是溃疡性结肠炎(UC)患者患结直肠癌的风险会增加。尽管5-氨基水杨酸(5-ASA)被广泛用于治疗UC以抑制结肠炎症,但尚未有研究使用动物模型来检验在结肠炎缓解期给予5-ASA对结肠炎相关癌症的化学预防作用。因此,我们在小鼠模型中研究了过氧化物酶体增殖物激活受体γ(PPARγ)配体和5-ASA对结肠炎相关结肠癌发生的可能抑制作用。
使用葡聚糖硫酸钠/氧化偶氮甲烷诱导的小鼠结肠癌模型,评估在结肠炎缓解期给予5-ASA和PPARγ配体对结肠炎相关结肠癌发生的化学预防作用。
用5-ASA治疗的小鼠中的肿瘤数量显著低于对照小鼠。此外,治疗小鼠中的肿瘤大小也显著小于对照小鼠。相比之下,用PPARγ配体治疗的小鼠在肿瘤数量或大小上未观察到显著抑制。5-ASA治疗小鼠的肿瘤细胞中增殖细胞核抗原标记指数显著小于对照,表明5-ASA减少了肿瘤细胞增殖。
我们的结果显示,在结肠炎缓解期给予5-ASA可显著抑制小鼠模型中结肠炎相关癌症的发生,这表明即使对于处于缓解期的UC患者,采取化学预防策略也具有临床重要性。