HGF Hepatic Regeneration Therapy Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
Oncol Rep. 2011 Aug;26(2):335-41. doi: 10.3892/or.2011.1294. Epub 2011 May 4.
Hepatocyte growth factor (HGF), which facilitates the repair of injured mucosa, has the potential to be a new therapeutic agent for inflammatory bowel disease (IBD). However, given that the incidence of colorectal cancer increases continuously with disease duration in patients with IBD, the fact that HGF is a potent mitogen for intestinal epithelial cells may further heighten the risk of bowel cancer in this patient population. In this study, we examined the effects of recombinant HGF on colorectal cancer development in mice with or without experimentally induced colitis. Although HGF stimulated proliferation of colonic epithelial cells in normal mucosa, the development of colorectal cancer induced by repeated injection of azoxymethane (AOM) was significantly inhibited by HGF treatment. In a mouse model of colitis-associated cancer, colorectal cancer frequently developed despite only a single injection of AOM prior to three cycles of dextran sulfate sodium administration. However, HGF treatment significantly facilitated the repair of injured mucosa, leading to inhibition of colorectal cancer development in a dose-dependent manner. Thus, HGF-induced repair of injured mucosa inhibits rather than accelerates the development of colorectal cancer, and these results also suggest the importance of blocking the cycles of mucosal injury and repair to prevent colitis-associated colorectal cancer.
肝细胞生长因子（HGF）有助于修复受损的黏膜，有可能成为治疗炎症性肠病（IBD）的新疗法。然而，鉴于 IBD 患者的结直肠癌发病率随着疾病持续时间不断增加，HGF 是肠上皮细胞的有效有丝分裂原，这可能会进一步增加该患者群体患肠癌的风险。在这项研究中，我们研究了重组 HGF 对伴有或不伴有实验性结肠炎的小鼠结直肠癌发展的影响。虽然 HGF 刺激正常黏膜中的结肠上皮细胞增殖，但 HGF 处理可显著抑制反复注射氧化偶氮甲烷（AOM）诱导的结直肠癌的发展。在结肠炎相关癌症的小鼠模型中，尽管在给予三周期葡聚糖硫酸钠之前仅注射一次 AOM，但仍常发生结直肠癌。然而，HGF 处理显著促进了损伤黏膜的修复，从而以剂量依赖性方式抑制了结直肠癌的发展。因此，HGF 诱导的损伤黏膜修复抑制而不是加速结直肠癌的发展，这些结果还表明阻断黏膜损伤和修复循环以预防结肠炎相关结直肠癌的重要性。
