Study On The Immuno-modulation Of Diosgenin And Antitumor Metastasis Mechanism

Diosgenin is a naturally occurring steroidal saponin, widely exists in many Trigonella and Dioscorea in medicinal plants,and is a precursor in the synthesis of various kinds of hormone drugs, widely use in the pharmacertical industry.Research shows that diosgenin has a widely pharmacological activities, have been used as antihypercholesterolemia, antihyperglycemic and anti-diabetic durg use. A series of animal experiments and mechanism show that diosgenin could enhance phagocytic capability of macrophages, and induced them to apoptosis,such as osteosarcoma, colon cancer, leukemia, liver cancer and breast cancer. Therefore, diosgenin possess tumor therapeutic potential. However, the effect of diosgenin on cancer metastasis remains poorly understood, its effect may be related to multiple molecular and celluar targets.This research investigates the immuno-modulation of diosgenin from two angles of in vitro and in vivo to clarify the new mechanism of antitumor effect of diosgenin. The study found that diosgenin could dsignificantly inhibit the growth of S-180 sarcoma in mice, and significantly increase the thymus and spleen of tumor weight of mice,promote the secretion of serum tumor necrosis factor TNF-α.Diosgenin in vitro can promote lymphocyte transformation, enhance the phagocytosis of macrophage, obviously promote macrophages to secrete NO and TNF-α.The results of the study indicate that diosgenin could promote specific and non-specific cellar immunity reaction, and the anti-tumor effects of diosgenin were achieved by immuno-stimulating properties instead of direct cytotoxicity.Diosgenin possess tumor therapeutic potential. However, the effect of diosgenin on cancer metastasis remains poorly understood. In this study, we performed in vitro experiments to investigate the inhibitory activity of diosgenin on human breast cancer MDA-MB-231 cell migration, and reveal the possible mechanism. Diosgenin caused a marked inhibition of cell migration in MDA-MB-231 cell by transwell assay. In addition, diosgenin significantly impacted MDA-MB-231 cell migratory behavior under real-time observation. We also found diosgenin significantly inhibited actin polymerization, Vav2 phosphorylation and Cdc42 activation, which might be, at least in part, attributed to the anti-metastatic potential of diosgenin. These findings reveal a new therapeutic potential of diosgenin for human breast cancer metastasis therapy.Our previous study showed that diosgenin has low oral bioavailability because of its strong fat-soluble feature. The drug must first be dissolved in gastrointestinal digestive liquid before absorption, and then to passive diffusion or active transport by way of digestive tract mucosa, enter the blood circulation. Insoluble drug in the digestive liquid of dissolution was usually the absorption rate limiting stage. However, such as superfine grinding technology, self micro emulsifying technology, liquid solid compression only technology means to improve pharmacy solubilization of insoluble drug solubility in certain degree and range, so only in drug design stage through the modification of its structure, can greatly improve the solubility and dissolution of drug. In this study, diosgenin succinic anhydride and amino acetic acid by esterification of the connection, and obtained two derivatives of 3β-diosgenin succinic acid ester and 3β-diosgenin amino acetate, and characterized their structures, in order to improve the diosgenin oral bioavailability study provides the scientific on the basis.