Inhibition by Losartan on ascites in a nude mouse model of human ovarian cancer / 中华老年医学杂志

ABSTRACT

Objective:To investigate whether Losartan can inhibit the formation of ascites in a nude mouse model of ovarian cancer by improving lymphatic drainage.Methods:Eight-week-old nude mice were randomly divided into 3 groups with 24 mice in each group.The blank control group received no treatment.Mice in the other two groups were given orthotopic transplantation of SKOV3 IP1-Gluc human ovarian cancer cells.Peritoneal tumor growth was monitored by peripheral blood Gluc levels, and mice were enrolled when the blood Gluc level reached 1×10 6 relative light units.Twenty-two nude mice were in the control group and 23 in the Losartan treatment group.Mice were sacrificed on the 28 th day after cancer cell implantation.Tumor tissues and diaphragm were removed, and the volume of ascites was measured after suction.Sirius Red, αSMA and Collagen 1 staining were used to detect the contents of extracellular matrix collagen and fibroblasts.Lymphangiography was used to examine the diaphragmatic lymphatic morphology, and intraperitoneal injection of fluorescent microspheres was used to visualize the distribution of fluorescent microspheres in diaphragmatic and mediastinal lymph nodes to estimate the function of diaphragmatic lymphatic drainage. Results:Losartan treatment significantly reduced the formation of ascites in the nude mouse model of ovarian cancer( P<0.05). Intratumoral contents of collagen(sirius red positive area, Collagen 1 content)and fibroblasts(αSMA positive area)were significantly reduced in the Losartan treatment group(all P<0.05). Compared with normal nude mice, the diaphragm lymphatic vessels were dilated and the structure was disordered in the control group.In the Losartan treatment group, the morphology and distribution of lymphatic vessels in the diaphragm improved and tended to normalize, as did the drainage function of lymphatic vessels. Conclusions:Losartan can inhibit the formation of extracellular matrix, reduce the extracellular matrix content of ovarian cancer cells, reduce solid pressure, relieve the oppressive effect on lymphatic vessels, improve lymphatic drainage and reduce ascites formation.