Effect Of Vascular Endothelial Growth Factor(VEGF) Antisense CDNA On The Expression Of VEGF And Its Receptor In Non-small Cell Lung Cancer In Nude Mice Model And Its Significance

The effective method in treating lung cancer is being probed now. Gene therapy is gradually accepted by more and more clinician. Antisense gene technique is one the most important methods in gene therapy. Tumor growth depend on angiogenesis. In order to provide information for gene therapy in anti-angiogenesis of lung cancer, we study the effect of vascular endothelial growth factor(VEGF) antisense cDNA on the expression of VEGF and its receptor, investigate the relationship between tumor growth and secretive path of VEGF. METHODSXenograft tumors were established in 40 nude mice weighing 18-22grams bysubcutaneous injection of human calu-6 non-small cell lung cancer cells. They were divided into 4 groups. Group A is control group, the mice weren't given any treatment. Group B is empty vector group. In group C, the mice were treated with carbolatin. In group D, the mice were treated with VEGF antisense cDNA-Lipofectamine complex. We mesure the volume and wight of tumors periodically in different groups. After 10 weeks, all nude mice were killed. Tumor sections were stained by immunohistochemistry for VEGF, flt-1, flk-1, CD31 and PCNA. VEGFmRNA was detected by in situ molecular hybrization. The ultrastructure of tumor cells were observed by electrnic microscope. RESULTSLower expression of VEGFmRNA, VEGF, flt-1, flk-1, CD-31 and PCNA were observed in the group of tumors treated by VEGF antisense cDNA(P < 0.001). Volume of tumors in the group treated by VEGF antisense cDNA is smaller than other groups(P < 0.001). The expression of VEGFmRNA was positively related to the expression of VEGF protein(P=0.01). The expression of VEGF was positively related to the expression of flt-1, flk-1, CD31 and the volume of tumors(P=0.01).CONCLUSIONSVEGF antisense cDNA can effectively down-regulate the expressipn of VEGF and its receptor in tumor's and vascular endothelial cell. It reduce angiogenesis, inhibit the growth of tumors. The results in animals manifest that it is an effective gene therapy in anti-angiogenesis in non-small cell lung cancer. Expression of VEGF influence the expression of its receptor. VEGF can help the growth of tumors by two pathes, autocrine and bypass secretion. Microvessel density, expression of VEGF and its receptor in rumors can act as a prognostic factor for patients. VEGF antisense cDNA has less side effects than chemotherapy's.