Enhancement of cancer cell radiosensitivity by adenovirus vector carrying siRNA of Survivin gene
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Abstract:
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 tumorbearing mice. Methods: The specific siRNA of Survivin gene was designed and synthesized, and a recombinant adenovirus AdEGFPsiRNA 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 AdEGFPsiRNA), siRNA(-) group (injected every other day with AdEGFPsiRNA\[-\], 2×108 pfu/100 μl 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 AdEGFPsiRNA 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 AdEGFPsiRNA, with the inhibition rate being 56.2%. The inhibition rate in AdEGFPsiRNA 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.