Study on Tumor Blood Vessel Normalization to Enhance the Antitumor Effect of Adriamycin Induced by Candesartan

OBJECTIVE To explore the enhanced anti-tumor effect of adriamycin based on normalization of tumor blood vessels induced by candesartan. METHODS 4T1 breast cancer cells and fibroblasts 3T3 cells were cultured and mixed at a ratio of 1:3 and inoculated subcutaneously in nude mice to construct a nude mouse model bearing tumors. The inhibitory effects of candesartan, adriamycin, and adriamycin combined with candesartan on tumor growth were compared. Tumor suppression rate was calculated. The contents of type I collagen, hyaluronic acid and TGF-β1 in rats serum were detected by enzyme linked immunosorbent assay, and the expression of CD31, TSP-1 and HIF-1α were detected by immunohistochemistry, the related indexes of tumor vascular normalization were observed. RESULTS Candesartan, adriamycin, adriamycin combined with candesartan could inhibit the growth of tumor. Among them, adriamycin combined with candesartan group significantly inhibited tumor growth better than the other two groups. The percentage of tumor inhibition rate of candesartan group, adriamycin group, adriamycin combined with candesartan group was 33.33%, 40.00%, 53.33%, respectively. Compared with other experimental groups, the content of type I collagen, hyaluronic acid and TGF-β1 in adriamycin combined with candesartan group decreased significantly, while the expression of CD31 and HIF-1α in adriamycin combined with candesartan group decreased significantly, and the expression of TSP-1 increased. CONCLUSION Candesartan may improve the antitumor effect of adriamycin by reducing the fibrosis of tumor tissue, reducing vascular density and inducing the normalization of tumor blood vessels.