Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma.
Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma.
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DOI：
10.18632/oncotarget.17264
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Wan Q
中科院分区：
文献类型：
--
作者：
Peng QX;Han YW;Zhang YL;Hu J;Fan J;Fu SZ;Xu S;Wan Q
血管生成是由血管表皮生长因子（VEGF）配体激活血管表皮生长因子受体-2（VEGFR-2）引发的。VEGFR-2的过表达促进鼻咽癌的生长。阿帕替尼（YN 968 D1）是一种高选择性的VEGFR-2抑制剂，但其对鼻咽癌的治疗作用尚未见报道。在本研究中，将CNE-2 NPC细胞异种移植到132只裸鼠中，这些裸鼠用单独施用或与顺铂（DDP）组合施用的阿帕替尼的6种药物方案之一治疗。通过组织病理学、免疫组织化学（VEGFR-2和CD 31）、末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）、微量18 F-FDG PET/CT成像和存活曲线确定治疗方案对肿瘤生长、微血管形成、细胞凋亡和代谢反应以及小鼠存活的影响。阿帕替尼单独给药可抑制肿瘤生长，降低微血管密度，促进肿瘤细胞凋亡。与单独和序贯给药治疗相比，阿帕替尼和顺铂同时治疗的肿瘤表现出显著增加的肿瘤生长抑制、延长的生存时间、降低的VEGFR-2表达、降低的微血管密度和细胞凋亡频率。同时接受阿帕替尼和顺铂治疗的肿瘤的FDG摄取最低。总之，阿帕替尼和顺铂同时给药与单独治疗相比改善了疗效，这也导致了与序贯给药方案相比的疗效改善。VEGFR-2是阿帕替尼治疗NPC疗效的重要预测指标。
Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP). The impact of treatment regimens on the growth, microvascularization, apoptosis, and metabolic response of tumors, as well as mouse survival was determined by histopathology, immunohistochemistry (VEGFR-2 and CD31), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), micro 18F-FDG PET/CT imaging and survival curves. Administration of apatinib alone inhibited tumor growth, reduced microvascular density, and facilitated the apoptosis of tumors. Tumors treated simultaneously with apatinib and cisplatin exhibited significantly-increased inhibition of tumor growth, prolonged survival time, decreased expression of VEGFR-2, reduced microvascular density, and frequency of apoptosis over standalone and sequential administration therapy. Tumors treated simultaneously with apatinib and cisplatin had the lowest uptake of FDG. Taken together, the simultaneous administration of apatinib and cisplatin improves the therapeutic efficacy over standalone treatments, which also led to improved efficacy over sequential administration regimens. VEGFR-2 is an important predictive marker for efficacy of apatinib treatment of NPC.
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影响因子：
4
作者：
Ji G;Hong L;Yang P
通讯作者：
Yang P
榄香烯注射液诱导自噬保护人肝癌细胞免于饥饿和凋亡
DOI：
10.1155/2014/637528
发表时间：
2014
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
The Journal of experimental medicine
影响因子：
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作者：
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影响因子：
158.5
作者：
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DOI：
10.1016/j.jchromb.2012.03.027
发表时间：
2012-05-01
影响因子：
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作者：
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