A Novel Peptide for Simultaneously Enhanced Treatment of Head and Neck Cancer and Mitigation of Oral Mucositis.
A Novel Peptide for Simultaneously Enhanced Treatment of Head and Neck Cancer and Mitigation of Oral Mucositis.
复制标题
DOI：
10.1371/journal.pone.0152995
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Toback FG
中科院分区：
文献类型：
--
作者：
Chen P;Mancini M;Sonis ST;Fernandez-Martinez J;Liu J;Cohen EE;Toback FG
我们从胃窦粘膜蛋白(AMP)-18中提取了一种新的21个氨基酸的多肽，它介导了培养的正常上皮细胞的生长促进作用，并在动物模型中减轻了辐射诱导的口腔粘膜炎，同时抑制了癌细胞的体外功能。本研究的目的是在临床相关的头颈癌动物模型中评价AMP多肽对肿瘤生长和放射性口腔粘膜炎的双重潜在治疗作用。将生物发光的SCC-25HNC细胞注射到舌前部，然后对形成的肿瘤进行局部放射治疗。用活体成像系统评估肿瘤大小，并比较接受AMP多肽或赋形剂(对照组)治疗的动物的口腔粘膜炎程度。AMP多肽/放射治疗队列中的肿瘤与单纯放射治疗的肿瘤相比，显示出生长受到抑制，而AMP多肽治疗推迟了放射治疗引起的口腔粘膜炎的发病并减轻了严重程度，这表明AMP肽与放射治疗之间存在协同作用。AMP-18可促进受损粘膜上皮细胞的生长和修复，同时抑制HNC细胞的增殖，其机制之一可能是对细胞凋亡的不同影响。RNA微阵列分析确定了AMP-18在HNC和未转化细胞中差异靶向的途径。这些观察结果证实了这样一个观点，即正常细胞和肿瘤细胞对常见生物刺激的反应可能不同，在AMP-18病例中利用这一发现可能提供临床相关的机会。
We have characterized a novel 21 amino acid-peptide derived from Antrum Mucosal Protein (AMP)-18 that mediates growth promotion of cultured normal epithelial cells and mitigates radiation-induced oral mucositis in animal models, while suppressing in vitro function of cancer cells. The objective of this study was to evaluate these dual potential therapeutic effects of AMP peptide in a clinically relevant animal model of head and neck cancer (HNC) by simultaneously assessing its effect on tumor growth and radiation-induced oral mucositis in an orthotopic model of HNC. Bioluminescent SCC-25 HNC cells were injected into the anterior tongue and tumors that formed were then subjected to focal radiation treatment. Tumor size was assessed using an in vivo imaging system, and the extent of oral mucositis was compared between animals treated with AMP peptide or vehicle (controls). Synergism between AMP peptide and radiation therapy was suggested by the finding that tumors in the AMP peptide/radiation therapy cohort demonstrated inhibited growth vs. radiation therapy-only treated tumors, while AMP peptide-treatment delayed the onset and reduced the severity of radiation therapy-induced oral mucositis. A differential effect on apoptosis appears to be one mechanism by which AMP-18 can stimulate growth and repair of injured mucosal epithelial cells while inhibiting proliferation of HNC cells. RNA microarray analysis identified pathways that are differentially targeted by AMP-18 in HNC vs. nontransformed cells. These observations confirm the notion that normal cells and tumor cells may respond differently to common biological stimuli, and that leveraging this finding in the case of AMP-18 may provide a clinically relevant opportunity.