Anti-tumor Effect Of Synthetic Short Peptide RLj-RGD4 In Mice Bearing Lewis Lung Cancer

ObjectiveTo investigate the function and mechanisms of short mutant rLj-RGD4 from the wild type rLj-RGD3 on the growth,the metastasis and lengthening the life time in mice bearing Lewis lung cancer.MethodsCulture Lewis lung cancer cells and establish the C57BL/6 mice model with Lewis lung cancer cells.The mice were randomLy divided into five groups:model group,rLj-RGD4 low dose?12.5?g/kg?,middle dose?25.0?g/kg?,high dose?50.0?g/kg?groups,and Doxorubicin(0.5 mg.kg^-1)group.Every group indicators were measured during when the drugs were continuously injected three weeks.Three weeks later,the mice were put to death and the volume and weight of tumors were measured.Compared with models,the anti-tumor effects of rLj-RGD4 on tumor growth were calculated and the pathological change of the tumor tissue was observed with HE staining method.3 weeks later,the average number of lung metastasis clones was counted to evaluate the anti-tumor effect of rLj-RGD4 on the inhibition of tumor metastasis.Compared with model group,the life time prolongation rate was calculated till the mice died.The mice tumor tissue section was labeled by CD34,and the tumor microvaculer was stained by immunohistochemical staining.The expression of FAK,p-FAK?ILK were detected by Western blotting in the tumor tissue of every group.ResultsCompared with models,the inhibition rate of tumor weight was 19.7%?p<0.05?,29.7%?p<0.001?,57.8%in different dose of rLj-RGD4,and the inhibition rate of tumor volume was 9%?p<0.01?,35.1%?P<0.001?,46.2%?P<0.001?.In spontaneous lung cancer,the transfer inhibition rate was 74.1%?93.3%?97.8%?P<0.01?;the hematogenous metastasis inhibition rate was 39.9%,57%,74.6%;the rate of life extension was 29.6%?P<0.05?,41.9%?P<0.01?,62.4%?P<0.01?;rLj-RGD4 can inhibit micro neovascularization in a dose-dependent,and induce apoptosis.In the tumor tissue,rLj-RGD4can inhibit the expression and phosphorylation of FAK,and cause the decline of ILK.ConclusionrLj-RGD4 can inhibit the growth and metastasis in mice bearing Lewis lung cancer in a dose-dependent,and can extend the life of mice bearing Lewis lung cancer;the mechanism of its anti-tumor effects is related to inducing tumor apoptosis and inhibiting neovascularization;its molecule mechanism involves the inhibition of the integrin signaling.