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The tumour neovasculature-homing dimeric peptide GX1 demonstrates antiangiogenic activity in the retinal neovasculature.
Luo, Yingying; Yin, Jipeng; Fang, Rutang; Liu, Jingtao; Wang, Lu; Zhang, Haiping; Zhang, Ming; Lei, Zhijie; Liang, Shuhui; Cui, Wei; Zhang, Zhiyong; Wu, Kaichun; Hui, Xiaoli.
Afiliación
  • Luo Y; Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China.
  • Yin J; State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi Xi'an, 710032, China.
  • Fang R; State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi Xi'an, 710032, China; Department of Gastroenterology, Affiliated No. 986 Hospital of Xijing Hospital, Fourth Military Medical University, Shaanxi Xi'an, 710032, China.
  • Liu J; Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China; Department of Nuclear Medicine, Affiliated No. 986 Hospital of Xijing Hospital, Fourth Military Medical University, Shaanxi Xi'an, 710032, China.
  • Wang L; Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China.
  • Zhang H; Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China.
  • Zhang M; Department of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China.
  • Lei Z; State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi Xi'an, 710032, China.
  • Liang S; State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi Xi'an, 710032, China.
  • Cui W; Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China.
  • Zhang Z; Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China. Electronic address: zhangzyxj1983@126.com.
  • Wu K; State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi Xi'an, 710032, China. Electronic address: kaicwu@fmmu.edu.cn.
  • Hui X; Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Xi'an, 710061, China. Electronic address: hxlljt@126.com.
Eur J Pharmacol ; 912: 174574, 2021 Dec 05.
Article en En | MEDLINE | ID: mdl-34662566
Identification of molecules specific to the retinal neovasculature will promote antiangiogenic therapy with enhanced targeting ability. The specificity of phage-displayed peptide GX1 (a cyclic 7-mer peptide motif CGNSNPKSC) to gastric cancer neovasculature has been extensively confirmed both in vitro and in vivo. To investigate the potential application of GX1 in antiangiogenic therapy targeting retinal angiogenesis-related diseases, we performed immunohistochemistry and immunofluorescence analyses. GX1 demonstrated positive staining in the retinal neovasculature in an oxygen-induced mouse model of retinopathy (OIR) as well as in rat retinal microvasculature endothelial cells (RMECs), confirming the major role of the GX1 receptor during retinal angiogenesis. Dimeric GX1 was synthesized to increase the binding affinity to the GX1 receptor, and the antiangiogenic effects were examined in RMECs in vitro and the retinal neovasculature in the OIR in vivo. Cell proliferation was evaluated using a Cell Counting Kit-8 (CCK-8) assay, revealing that compared with the GX1 monomer, dimeric GX1 significantly inhibited RMEC proliferation (P < 0.05). This finding may be attributed to the enhanced (P < 0.05) apoptosis induced by dimeric GX1 in RMECs based on results obtained from TUNEL, flow cytometric and cell cycle analyses. In RMECs, in vitro cell migration and tube formation were significantly inhibited following exposure to dimeric GX1. Intravitreal administration of dimeric GX1 resulted in a greater reduction in the retinal neovascularization in vivo than administration of the GX1 monomer (P < 0.05). In conclusion, dimeric GX1 showed greater inhibition of angiogenesis than monomeric GX1 and could be a promising agent for antiangiogenic therapy in retinal angiogenesis-related diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Neovascularización Retiniana / Inhibidores de la Angiogénesis / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Neovascularización Retiniana / Inhibidores de la Angiogénesis / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos