Survivin ASODN suppresses vasiformation in xenograft of colorectal cancer cells in nude mice

Objective To investigate the effect of antisense oligonucleotide (ASODN) against survivin on the apoptosis and vasiformation in nude mice after colorectal cancer cells transplantation. Methods After the establishment of the xenograft model of colorectal cancer in nude mice, the 24 animals were randomized into 4 groups with 6 mice in each group, that is, control group, Lipofectamine group, Lipofectamine+SODN group and Lipofectamine+ASODN group. Lipofectamine, SODN or ASODN was directly injected into the corresponding xenograft in 1, 4 and 8 d after tumorigenesis. The final weight of tumor mass was measured to calculate the suppression rate of tumor. The tumor tissues were morphologically observed by HE staining, the expression of survivin was measured by immunohistochemical method to calculate the microvessel density (MVD), and the apoptosis of tumor cells was detected by TUNEL. Results There was significant difference in the final weight of tumor mass in Lipofectamine+ASODN group with the other groups (P0.05), and the pathological observation showed that the growth of tumor cells was inhibited in this group. The tumor mass of this group showed necrosis in the lamellar zone and infiltration of massive inflammatory cells. The MVD of tumor was 19.57±3.37 in control group, 21.94±4.41 in Lipofectamine group, 20.49±3.91 in Lipofectamine+SODN group, and 11.30±2.79 in Lipofectamine+ASODN group. Significant difference was seen between Lipofectamine+ASODN group with the other groups (P0.05). The apoptotic index (AI) was 3.53±1.89, 3.86±2.14, 4.47±2.30, and 28.45±2.76 respectively for above mentioned groups. There was also significant difference between Lipofectamine+ASODN group with the other groups (P0.05). Conclusion Survivin ASODN inhibits significantly the expression of vascular endothelial growth factor (VEGF), induces the apoptosis of endothelial cells and the degeneration of capillaries, and thus suppresses the growth of tumor.