Effect and mechanism analysis of siRNA in inhibiting VEGF and its anti-angiogenesis effects in human osteosarcoma bearing rats

X.-Z. Zhu, J. Mei

Department of Orthopedic Surgery, Tongji Hospital, Tongji University, Shanghai, China. xiaozhong.zhu@163.com

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• Oncology

OBJECTIVE: To explore the effect of siRNA in inhibiting vascular endothelial growth factor (VEGF) expression in tumor cells from human osteosarcoma bearing rats and its anti-angiogenesis effect, to further study the reliability, effectiveness and safety of VEGF as a therapeutic target in treating osteosarcoma.

MATERIALS AND METHODS: After treatment, the long diameter and short diameter of tumor lesion were detected by Vernier caliper, and the tumor volume and tumor inhibition rate were calculated. The whole-body fluorescence imaging was used to detect the general morphology and volume change of tumor lesion before and after treatment. The rats were killed after treatment, RT-PCR and Western blot were used to detect VEGF expression. MTT was used to detect the proliferative ability of tumor cells in vitro.

RESULTS: Three chemotherapies could inhibit the growth of tumor lesion, the decrease of tumor volume was significant (p < 0.05), the therapeutic effect in Ad-VEGF-siRNA + neoadjuvant chemotherapy group was better than the other two groups, the differences were statistically significant (p < 0.05). Furthermore, the three chemotherapies could inhibit the invasiveness of tumor cells, which was most significant in Ad-VEGF-siRNA + neoadjuvant chemotherapy group (p < 0.05).

CONCLUSIONS: The growth of tumor tissue in osteosarcoma bearing rats is inhibited in Ad-VEGF-siRNA group, Ad-VEGF-siRNA + neoadjuvant chemotherapy group and Ad-VEGF-siRNA + anti-angiogenesis chemotherapy group. The effect in Ad-VEGF-siRNA + neoadjuvant chemotherapy is more significant than simple biological therapy or Ad-VEGF-siRNA + anti-angiogenesis chemotherapy.

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