Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma

• Published in: Journal of experimental & clinical cancer research 2016-11, Vol.35 (1), p.171-171, Article 171
• Main Authors: Kim, Dong Yoon, Choi, Jeong A, Koh, Jae-Young, Yoon, Young Hee
• Format: Article
• Language: English
• Subjects: Aflibercept; Analysis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Animals; Apoptosis; Cancer; Care and treatment; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; Choroidal invasion; Coculture Techniques; Health aspects; Human Umbilical Vein Endothelial Cells; Humans; Injections, Intraperitoneal; Mice; Neoplasm Invasiveness; Receptors, Vascular Endothelial Growth Factor - administration & dosage; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - pharmacology; Retinal Neoplasms - blood supply; Retinal Neoplasms - drug therapy; Retinoblastoma; Retinoblastoma - blood supply; Retinoblastoma - drug therapy; Treatment; Xenograft Model Antitumor Assays
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-016-0451-7

To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma. Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers. In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm vs. 747.87 ± 118.83 mm , respectively, P