Adrenomedullin Antagonist AM22-52 Suppresses Growth Of Human Ovarian Cancer Cells In Nude Mice

ObjectiveOvarian cancer is one of the common malignant tumors in female genital organs, but the mortality rate ranks first in gynecological tumors. Mostly, ovarian cancer is found in their late period, so surgery and chemotherapy treatment effects are poor. The five-year survival rate of ovarian cancer ranges from 25% to 30%. Therefore, the search for new drugs and effective role target to make earlier diagnosis and treatment is the current focus of the study. Adrenomedullin (AM) is a multifunctional peptide firstly found and isolated by Kitamura in human adrenal pheochromocytoma, which has been shown an important role in human tumorigenesis, invasion and metastasis mechanisms. AM22-52, the endogenous antagonist of AM, can block the specific receptor of AM. Vitro and vivo experiments in pancreatic cancer, breast cancer, glioblastoma and other malignant tumors have been shown that, AM22-52 suppresses tumor cell growth and migration by inhibiting tumor angiogenesis and increasing apoptosis.In preliminary experiments, we confirmed that AM22-52significantlysuppressed the proliferation of ovarian cancer cells CAOV3 and shew a dose-effect relationship by MTT assay. Our study is to observe the suppression effect of AM22-52 on growth of human ovarian cancer in nude mice.Methods1. Cell source and experimental animalsHuman ovarian cancer cells line, HO-8910 was purchased from Cell Resource Center of Life Sciences in Shanghai. BALB/c, nu/nu mice, female,4-6 weeks, weight 18～20g, SPF (specific pathogen free) grade, were offered by Shanghai Slac Laboratory animal center.2. MethodsThe human ovarian cancer cells line HO-8910 was subcutaneously implanted in nude mice. Mice bearing HO-8910 tumors were randomly divided into two groups (n= 15), and treated with AM22-52(20μg,0.2ml) and PBS (0.2ml) using intratumoral injection every 3 days for 4 times. The sizes of the human ovarian cancer xenografts were determined by measuring the tumor volumes. The mean tumor weights were compared by inhibition rate.3. Statistical analysisExperimental data were shown byχ±s. Software SPSS 13.0 was applied to make statistical analysis. Data were analyzed by t test. P<0.05 was considered as statistical significance.ResultsThe mean tumor volume in the AM22-52 group and control group were (28.38±3.77) mm3 and (175.72±4.16) mm3 respectively after 10 days of treatment, and the mean tumor weight were (48.3±6.41) mg and (299.06±7.06) mg respectively. The mean volume and weight of the tumors in the AM22-52 group was significantly reduced compared with the control group (P<0.05). Inhibition rate was 83.8%.ConclusionsAM22-52 shew the suppression effect on growth of human ovarian cancer cells in nude mice.