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.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the inhibition effects of polypeptide extract from scorpion venom (PESV) combined 5-fluorouracil (5-Fu) on vasculogenic mimicry (VM) of H2 hepatoma carcinoma cells in mice and its possible mechanisms.</p><p><b>METHODS</b>The H22 carcinoma cell suspension was subcutaneously inoculated into 60 Kunming mice. Then tumor-bearing mice were randomly divided into three groups, i.e., the control group, the 5-Fu group, and the combination group (PESV +5-Fu), 20 in each group. The tumor volume was measured once every other day after 14 successive days of intervention. Then the tumor volume growth curve was drawn, and the tumor inhibitory rate was calculated. The morphological changes of the tumor tissue were observed by HE staining. The VM density of each tumor tissue were detected by immunohistochemical assay and periodic acid-schiff stain (PAS). The protein expression levels of hypoxia inducible factor-la (HIF-la) and matrix metalloproteinase-2 (MMP-2) were detected using immunohistochemical assay. The gray value was semi-quantitatively analyzed using LeicaQwinV3 Image Analysis Software.</p><p><b>RESULTS</b>The growth of H22 hepatoma transplantation tumor was inhibited more obviously in the combination group and the 5-Fu group than in the control group (P <0.05). There was statistical difference in the tumor weight and the tumor volume between the combination group and the 5-Fu group (P <0.05). Immunohistochemical assay and PAS showed that the VM density was obviously lower in the combination group than in the control group and the 5-Fu group (P <0.01). Compared with the control group, the protein expressions of HIF-la and MMP-2 significantly decreased in the combination group (P <0.01).</p><p><b>CONCLUSIONS</b>PESV combined 5-Fu could inhibit the generation of VM of H22 hepatoma transplantation tumor in mice. Its mechanisms might be associated with inhibiting the expressions of HIF-lalpha and MMP-2 in the microenvironment of tumors.</p>