Inhibitory effects of phosphorothioate-modified antisense VEGF oligodeoxynucleotides formulated in cationic liposome on angiogenesis and metastasis of lung cancer / 中国免疫学杂志

ABSTRACT

Objective:The study aims to investigate whether phosphorothioate-modified antisense vascular endothelial growth factor oligodeoxynucleotides(VEGF ASODN)micro-encapsulated in cationic liposome could inhibit angiogenesis and metastasis of lung cancer.Methods:The phosphorothioate-modify VEGF ASODN, VEGF SODN(sense oligodeoxynucleotides) and VEGF MODN(mismatch oligonucleotides)micro-encapsulated in cationic liposome were added into in vitro culture of Lewis lung carcinoma(LLC ) cells,respectively. Expression of VEGF protein was detected by immunohistochemistry staining. And the inhibitory effects on bovine aortic endothelial cell proliferation by conditioned media obtained from LLC cells treated with ODN were observed. 40 mice of Lewis lung cancer models were established and subsequently were randomized into 4 groups control group, ASODN group, SODN group,and MSODN group. Liposome, ASODN, SODN or MODN were given by twice a week for 4 weeks,respectively.The weights of subcutaneous tumors were measured. The rates of lung metastasis were detected, while the microvessel density(MVD) in tumor mass was detected by imuunohistochemistry staining. Peak systolic flow velocity(PS) and resistance index(RI) were measured with a sonographic scanner.Results:ASODN downregulated the expression of VEGF in LLC cells at the level of protein in vitro. The conditioned media obtained from LLC cells treated with ASODN significantly inhibited the proliferation of bovine aortic endothelial cells. ASODN significantly suppressed the growth of subcutaneous tumors and lung metastasis. MVD, PS and RI of VEGF ASODN group were remarkably different from those of other 3 groups(P