Enhancement of cancer cell radiosensitivity by adenovirus vector carrying siRNA of Survivin gene / 中国肿瘤生物治疗杂志

ABSTRACT

Objective:To construct a recombinant adenoviral vector carrying the specific siRNA of Survivin gene,and to observe its effect on the expression of Survivin gene and on the radiosensitivity of cancer cells in tumor-bearing mice.Methods:The specific siRNA of Survivin gene was designed and synthesized,and a recombinant adenovirus AdEGFP-siRNA was subsequently constructed.SMMC 7721 xenograft models were established with nude mice and were divided into the following 5 groups:siRNA+radiotherapy and siRNA groups(intratumoral injection of AdEGFP-siRNA),siRNA(-)group(injected every other day with AdEGFP-siRNA[-],2?108 pfu/100 ?l per time,total 5 times),pure radiotherapy group and blank control groups(injected with the same volume of normal saline).On day 10,12,14,and 16,the mice in siRNA+radiotherapy and pure radiotherapy groups were given 5 Gy/time radiotherapy.The tumor volumes were measured regularly.The expression of Survivin in tumor tissues was determined immunohistochemically.Results:Adenovirus AdEGFP-siRNA harboring the specific siRNA of Survivin gene and enhanced green fluorescent protein gene(EGFP)was successfully recombined.The growth of SMMC 7721 xenografts in nude mice was inhibited after injecting AdEGFP-siRNA,with the inhibition rate being 56.2%.The inhibition rate in AdEGFP-siRNA therapy + radiotherapy increased to 82.6%.Immunohistochemistry study showed that the specific siRNA markedly silenced the expression of Survivin gene in hepatocarcinoma cells.Conclusion:The specific siRNA can markedly silence Survivin gene and subsequently inhibit the growth of cancer;meanwhile,it can also increase the radiosensitivity of cancer cells so as to improve the treatment effect.