OBJECTIVETo study the effects of polypeptide extract from scorpion venom (PESV) alliance with chemotherapy on angiogenesis of Lewis lung carcinomas (LLC) and its mechanism.

METHODLLC cells suspension (4 x 10(6) cells/mL) were subcutaneously injected into 54 C57BL/6J mice in right armpits. Then the tumor-bearing mice were randomly divided into three groups: the control group, the chemotherapy group and the PESV group. Cyclophosphamide was used to establish the model of cancer. Chemotherapy and PESV were added to the PESV group. Every 7 days, 6 mice of each group were executed, and the experiments were carried out for 28 days. The tumor volume and inhibitory rate were determined. Immunohistochemistry and RT-PCR were used to determine the expression of factor VIII, alpha-SMA, Dll4 and Notch1 in tumor tissue. Correlation analysis was used to identify the relationship of factor VIII and calculate microvessel density (MVD), alpha-SMA and vascular maturity.

RESULTThe inhibitory rate of PESV was 42.21%. Comparing with the chemotherapy group, the expression of tumor factor Dll4 and Notch1 in the PESV group were decreased significantly (P < 0.05). The expression of factor VIII and alpha-SMA in the chemotherapy group is lower than the control group (P < 0.05), while it's higher when compared with the PESV group (P < 0.01). Expression of Dll4 and Notch1 in the chemotherapy group at the 28th day were higher than the control group (P < 0.05), and the expression in the PESV group at the 21st day were significantly lower than the chemotherapy group (P < 0.05).

CONCLUSIONPESV could inhibit the angiogenesis of LLC. It might be attained by decreasing the level of angiogenic factors, that are factor VIII, alpha-SMA, Dll4 and Notch1 in tumor microenvironment.