Combination of adenovirus-mediated endostatin gene and chemotherapy in treatment of Lewis lung cancer in mice / 第二军医大学学报

ABSTRACT

Objective:To study the antitumor effect of combination therapy with adenoviral transfer of mouse endostatin gene and cyclophosphamide chemotherapy on mouse Lewis lung cancer.Methods:Mouse endostatin gene was cloned into repli-cation-defective adenovirus by virus recombination technology to construct Ad-mES,adenovirus vector coding mouse endo-statin gene,and then its biological activities were surveyed in vivo.Animal models of mouse Lewis lung carcinoma in C57BL/6mice were established and randomly divided into4groups(n=10)including control,chemotherapy,gene therapy,and chemotherapy+gene therapy group.Mice received cyclophosphamide150mg/kg s.c.3times a day in a21-d cycle for chemotherapy;control group received0.9%normal saline100?l.Ad-mES(6?10 9 pfu/100?l)were administrated by multi-spots intra-tumor injection to every mouse in gene therapy group and combination therapy group.The tumor sizes were mea-sured at different times points.The expression of endostatin after transfer was detected by Western blot and the microvessel density(MVD)of tumor was measured by immunohistochemical examination.Results:Higher titers of recombinant aden-oviruses(Ad-mES)were constructed.Combination therapy with Ad-mES and cyclophosphamide inhibited tumor growth(P