Mechanism of polypeptide from scorpion venom increasing inhibition of 5-fluorouacil on H22 hepatoma / 中草药

ABSTRACT

Objective: To explore the mechanism of polypeptide from scorpion venom (PSV) on increasing the inhibition of 5-fluorouacil (5-Fu) on H22 hepatoma. Methods: H22 hepatoma model was established through sc inoculating H22 cells suspension into 40 mice in right armpits. Then tumor-bearing mice were divided into five groups randomly on the day 7 after inoculating model, PSV (20 mg/kg), 5-Fu (15 mg/kg), low-dose PSV (5 mg/kg) + 5-Fu, and high-dose PSV (20 mg/kg) + 5-Fu groups, 10 mice in each group, continuously admininstered for 21 d. Tumor volumes were measured once every other day, then the curves of tumor growth were drawn and the tumor inhibitory rate was calculated; CD34 was used to mark capillary; Immunohistochemical assay was used to detect the protein expression changes of nuclear factor-kappa B (NF-κB), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF). Results: Compared with the model group, the growth of H22 hepatoma transplantation tumor in the combinational groups was obviously inhibited (P < 0.01); The microvessel density (MVD) and the protein expression of NF-κB, MMP-9, and VEGF in the two PSV groups were all decreased significantly (P < 0.01); Compared with 5-Fu group, the MVD and the protein expression of NF-κB, MMP-9, and VEGF in the high-dose PSV + 5-Fu group were also decreased (P < 0.01), while there was no significant difference between the low-dose PSV + 5-Fu group. Conclusion: PSV may increase the inhibition of 5-Fu on H22 hepatoma through blocking NF-κB pathway and reducing the expression of MMP-9 and VGF, which is beneficial to the inhibition of angiogenesis.