Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization

被引:51
作者
Weiss, Andrea [1 ,2 ]
van Beijnum, Judy R. [2 ]
Bonvin, Debora [1 ]
Jichlinski, Patrice [3 ]
Dyson, Paul J. [4 ]
Griffioen, Arjan W. [2 ]
Nowak-Sliwinska, Patrycja [2 ,3 ]
机构
[1] Swiss Fed Inst Technol, EPFL, Inst Bioengn, Med Photon Grp, CH-1015 Lausanne, Switzerland
[2] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Angiogenesis Lab, Amsterdam, Netherlands
[3] CHU Vaudois, Dept Urol, Lausanne, Switzerland
[4] Swiss Fed Inst Technol, EPFL, Inst Chem Sci & Engn, CH-1015 Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
angiogenesis inhibitors; axitinib; bevacizumab; combination therapy; endothelial cells; photodynamic therapy; sorafenib; sunitinib; synergy; tyrosine kinase inhibitors; MACULAR DEGENERATION; TUMOR VASCULATURE; CELL CARCINOMA; ANGIOGENESIS; COMBINATION; RADIATION; VERTEPORFIN; SUNITINIB; AXITINIB; RANIBIZUMAB;
D O I
10.1111/jcmm.12199
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Photodynamic therapy (PDT) is an effective clinical treatment for a number of different cancers. PDT can induce hypoxia and inflammation, pro-angiogenic side effects, which may counteract its angio-occlusive mechanism. The combination of PDT with anti-angiogenic drugs offers a possibility for improved anti-tumour outcome. We used two tumour models to test the effects of the clinically approved angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in combination with PDT, and compared these results with the effects of bevacizumab, the anti-VEGF antibody, for the improvement of PDT. Best results were obtained from the combination of PDT and low-dose axitinib or sorafenib. Molecular analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR-2 expression in tumour vasculature. Treatment with bevacizumab, although effective as monotherapy, did not improve PDT outcome. In order to test for tumour vessel normalization effects, axitinib was also applied prior to PDT. The absence of improved PDT outcome in these experiments, as well as the lack of increased oxygenation in axitinib-treated tumours, suggests that vascular normalization did not occur. The current data imply that there is a future for certain anti-angiogenic agents to further improve the efficacy of photodynamic anti-cancer therapy.
引用
收藏
页码:480 / 491
页数:12
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