Suppression of human glioblastoma in nude mice by siRNA Notch-1 gene therapy

Background and purpose:In recent studies, the Notch-1 gene has been found to play an important role in the development of human glioblastoma.Short interfering RNA(siRNA) was used to silence the Notch-1 gene and block its expression.The objective was to determine whether siRNA targeting Notch-1 would inhibit the formation and growth of tumors in nude mice that modeled human glioblastoma.Methods:The human glioblastoma cell line TJ905 were first cultured and transfected with Notch-1 siRNA or nonsense siRNA by OligofectamineTM.The TJ905 cells were divided into 3 groups:the Notch-1 siRNA transfected group, nonsense siRNA transfected group and the control group.Each group's cells were subcutaneously injected into 5 nude mice.The nude mice(males, 3-4 weeks old) were given subcutaneous injections of either 0.2 mL of transfected siRNA or with normal TJ905 cells suspended at a 1×107 cells/mL concentration in a DMEM medium without serum.One week later, when the tumors were palpable, they were directly injected with the Notch-1 siRNA complex, nonsense siRNA complex, or PBS every 4 days for 20 days.Tumor sizes were measured every 3 days and calculated by the formula:volume(mm3) =1/2 length×(width)2.After a 20-day follow-up period, the mice were exterminated.Immunohistochemistry was used to determine the expression of Notch-1 gene.Results:The final tumor volume was less in nude mice injected with Notch-1 siRNA(1 203±206) mm3 compared mice injected with the nonsense siRNA injection(2 241±401) mm3, P0.01 or PBS injection(2 309±466) mm3, P0.01.After the siRNA-Notch-1 transfection, the expression of Notch-1 gene decreased tumors in comparison to the other 2 groups(P0.05).Conclusion:The transfection of siRNA targeting Notch-1 could significantly inhibit tumor growth in mouse models with human glioblastoma.