阿西替尼对人口腔黏膜黑色素瘤裸鼠移植瘤血管生成拟态的作用探讨

doi:10.19438/j.cjoms.2018.04.002

中国口腔颌面外科杂志 ›› 2018, Vol. 16 ›› Issue (4): 296-301.doi: 10.19438/j.cjoms.2018.04.002

阿西替尼对人口腔黏膜黑色素瘤裸鼠移植瘤血管生成拟态的作用探讨

洪多¹, 顾子悦¹, 李江², 张志愿¹

1.上海交通大学医学院附属第九人民医院·口腔医学院口腔颌面-头颈肿瘤科,
2.口腔病理科, 国家口腔疾病临床研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011

收稿日期:2018-03-05 修回日期:2018-05-17 出版日期:2018-07-20 发布日期:2018-08-09
通讯作者: 张志愿,E-mail：zhzhy0502@163.com
作者简介:洪多（1992-）,男,硕士研究生,E-mail：china8male@sjtu.edu.cn
基金资助:
国家自然科学基金（81430012）

Axitinib inhibits oral mucosal melanoma growth through modulating vasculogenic mimicry in a patient-derived xenograft model

HONG Duo¹, GU Zi-yue¹, LI Jiang², ZHANG Zhi-yuan¹

1.Department of Oromaxillofacial Head and Neck Oncology,
2.Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology. Shanghai 200011, China;

Received:2018-03-05 Revised:2018-05-17 Online:2018-07-20 Published:2018-08-09

摘要/Abstract

摘要： 目的:探讨阿西替尼用于口腔黏膜黑色素瘤(oral mucosal melanoma, OMM）治疗的可行性。方法:取病理确诊的口腔黏膜黑色素瘤标本,构建病人源性小鼠移植瘤（patient-derived xenografts,PDX）模型。将PDX动物模型随机分为2组,分别给予阿西替尼和羧甲基纤维素钠处理,用药周期28 d。应用免疫组织化学染色和过碘酸雪夫反应双染法,检测各组肿瘤的血管拟态(vasculogenic mimicry,VM)、EphA2、MMP-2及HIF-1a等蛋白的表达。采用SPSS 23.0软件包对数据进行统计学分析。结果:与空白对照组相比,阿西替尼显著抑制肿瘤生长,VM数量、CD34⁺血管数量、EphA2及MMP-2蛋白表达水平显著降低;HIF-1a表达显著高于对照组。结论:阿西替尼对人口腔黏膜黑色素瘤小鼠具有较好的肿瘤生长抑制作用,主要机制可能为抗血管新生和VM形成。

关键词: 口腔黏膜黑色素瘤, 病人源性小鼠移植瘤模型, 血管拟态, 阿西替尼

Abstract: PURPOSE:To investigate the potential application of axitinib in treatment of oral mucosal melanoma (OMM). METHODS: After successful establishment of oral mucosal melanoma-bearing patient derived xenografts (PDX) model, 16 nude mice were randomly divided into control and experimental group. After oral administration of axitinib or sodium carboxymethylcellulose for 28 days, the tumors were assessed for histological and molecular features by immunochemical assay as well as growth status at least twice a week using vernier caliper. Vasculogenic mimicry was evaluated by immunochemistry and periodic acid schiff reaction (PAS) histochemical double-staining. SPSS 23.0 software package was used for statistical analysis. RESULTS: Compared to the control group, tumor volume, amount of vasculogenic mimicry and CD34-positive vessels in the axitinib group were significantly decreased after oral administration (P<0.05); meanwhile, the protein level of EphA2 and MMP-2 was significantly decreased in the axitinib group, and the expression of HIF-1a was significantly higher than the control group(P<0.05). CONCLUSIONS: Axitinib could be applied in target treatment of OMM.

Key words: Oral mucosal melanoma, Patient derived xenografts, Vasculogenic mimicry, Axitinib

中图分类号:

R739.85

洪多, 顾子悦, 李江, 张志愿. 阿西替尼对人口腔黏膜黑色素瘤裸鼠移植瘤血管生成拟态的作用探讨[J]. 中国口腔颌面外科杂志, 2018, 16(4): 296-301.

HONG Duo, GU Zi-yue, LI Jiang, ZHANG Zhi-yuan. Axitinib inhibits oral mucosal melanoma growth through modulating vasculogenic mimicry in a patient-derived xenograft model[J]. China J Oral Maxillofac Surg, 2018, 16(4): 296-301.

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阿西替尼对人口腔黏膜黑色素瘤裸鼠移植瘤血管生成拟态的作用探讨

Axitinib inhibits oral mucosal melanoma growth through modulating vasculogenic mimicry in a patient-derived xenograft model

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