Oncotarget

Research Papers:

Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma

Qiu-Xia Peng, Yun-Wei Han, Yan-Ling Zhang, Jie Hu, Juan Fan _, Shao-Zhi Fu, Shan Xu and Qiang Wan

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Oncotarget. 2017; 8:52813-52822. https://doi.org/10.18632/oncotarget.17264

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Abstract

Qiu-Xia Peng1,*, Yun-Wei Han1,2,*, Yan-Ling Zhang1, Jie Hu1, Juan Fan1, Shao-Zhi Fu1, Shan Xu1 and Qiang Wan3

1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China

2Shandong University, Shandong 250100, China

3Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China

*Yun-Wei Han contributed equally with Qiu-Xia Peng, and is the co-first author of this paper

Correspondence to:

Juan Fan, email: fj-joan@163.com

Keywords: nasopharyngeal carcinoma, apatinib, VEGFR-2, cisplatin, combined therapy

Received: December 14, 2016     Accepted: March 27, 2017     Published: April 20, 2017

ABSTRACT

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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