Effects Of Isorhamnetin On Protein Expression Of Vegf, Mmp-2 And Endostatin In Lewis Lung Cancer Mouse

Tumor angiogenesis is a marker for invasion, depending on the balance between angiogenesis suppressor and facilitating factors. This study established a Lewis lung cancer mouse model, on which the effect of isorhamnetin on the protein expression of vascular endothelial growth factor (VEGF), endostatin and matrix metalloproteinase- 2 (MMP-2) was measured for investigating the possible functional mechanisms. SPF grade C57BL/6 mice were treated with 50 mg/kg isorhamnetin and/or 2 mg/kg cisplatin. All groups received subcutaneous inoculation of Lewis lung cancer cells except control group. Drugs were delivered via intraperitoneal injection starting from day 2 after inoculation for 14 days. Tumor volume and suppressor rate were measured. Number of metastatic lesions at pulmonary lobe surface was counted, followed by HE staining and ELISA analysis of serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), VEGF and endostatin, along with immunohistochemistry (IHC) staining for measuring those proteins in tumor tissues. Model group had a larger tumor volume, lower serum IL-2, IFN-gamma and endostatin level, plus higher VEGF level (p<0.05 compared with control group). In metastatic tumor tissues, VEGF and MMP-2 protein expressions were up-regulated, accompanied with lower endostatin (p<0.05). Compared with model group, drug treatment decreased tumor volume, number of metastatic lesions and tumor cell density (p<0.05). Cotreatment resulted in higher tumor suppressing rate, serum IL-2, IFN-gamma and endostatin levels compared with single drug treatment, and lower serum VEGF, and VEGF/MMP-2 proteins in metastatic tumors (p<0.05). In conclusion, isorhamnetin inhibits tumor progression, possibly related with down-regulation of VEGF or MMP-2, as well as upregulation of endostatin.