Harada Koji, Ferdous Tarannum, Kobayashi Hiroaki, Ueyama Yoshiya
1 Yamaguchi University Graduate School of Medicine, Ube, Japan.
Integr Cancer Ther. 2018 Jun;17(2):423-430. doi: 10.1177/1534735417721014. Epub 2017 Jul 26.
Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.
抗癌药物引起的粘膜炎和皮炎是抗癌治疗常见的并发症。在本研究中,我们评估了含谷氨酰胺的要素膳安素(日本东京味之素制药有限公司)对5-氟尿嘧啶(5-FU)诱导的口腔粘膜炎和皮炎的体内治疗效果,并试图阐明其作用的潜在机制。分别通过5-FU处理并轻度擦伤仓鼠颊囊和裸鼠背部皮肤诱导口腔粘膜炎和皮炎。这些动物每天经胃管给予生理盐水、糊精或安素悬液(18千卡/100克),直至处死。在动物模型中,安素比糊精更有效地减轻了口腔粘膜炎和皮炎。此外,在体外研究了安素对人永生化角质形成细胞(HaCaT)的促生长作用。MTT法、伤口愈合试验和迁移试验表明,安素可增强HaCaT的生长、侵袭和迁移能力。酶联免疫吸附测定(ELISA)和蛋白质免疫印迹法显示,经安素处理的HaCaT中,成纤维细胞生长因子2(FGF2)表达上调。这些结果表明,安素对粘膜炎和皮炎的治疗有效,可能通过诱导FGF2和上皮再形成来加速粘膜和皮肤的恢复。