| Total Astragalus Extract (TAE),composed of astragalosides(AST) and astragalus polysaccharides(APS), are active compounds extracted from the root of Astragalus membranceus. As the tumor therapy at present is still unsatisfactory,finding new antitumor drugs is a urgent matter. The present study was therefore designed to investigate the antitumor effect of TAE both in vivo and in vitro and to explore its mechanisms of action at gross , celluar and molecular levels.The main points are concluded as follows:l.Inhibitory effect of TAE on implanted tumors in miceThe models of hepatoma (HepA),sarcoma(S180) and Ehrlich ascilic carcinoma(EAC) in mice were established.Experiments of studing the effect of TAE on the above three animal models were repeated by three times.The results showed that TAE(15,50,and 150mg kg-1, ig ,d1 to d11) could inhibit the growth of HepA tumor cells in mice at the inhibitory rate of 40.8%,45.8% and 43.0% ,respectively.It could also inhibit the growthof S180 tumor cells in mice at the inhibitory rate of 57.1%,54.5% and 45.9%,respectively.Also,TAE (50and 150mg kg-1,ig)could increase the number of the survival EAC mice whose life span exceeded20 days at the survival rate of 54.5% and 69.7%. These suggested that treatment with TAE could not only inhibit the growth of HepA and S180 in mice, but also could prolong the life span of EAC mice.In addition ,we also investigated the antitumor effects of two active parts TAE-AST and APS. The results showed that AST(3,10and30mg kg-1 ,ig ,d1 to d11) inhibited the growth of HepA in mice at the inhibitory rate of 35.2%, 40.8% and 43.6% respectively. It could also inhibit the growth of S180 in mice at inhibitory rate of 44.6% , 54.1% and 50.1%,respectively. Moreover, APS(12,40and 120mg kg-1 ,ig, d1 to d11) could inhibit the growth of HepA in mice at the inhibitory rate of 41.3% ,53.6% and 45.3%, respectively.These suggested that AST and APS are both active parts of TAE in tumor-therapy.2.1mmunomodulatory effect of TAEThe immunosuppressine model induced by Cyclophosphamide (CTX) or 5-Fluorouracil (5-Fu) in normal and tumor bearing mice were established to investigate the immunomodulatory effect of TAE. The results showed that TAE(50 and 150mg kg-1 ,ig ,d1 to d11) could enhance the thymus index in normal or S180 tumor bearing mice suppressed by CTX. TAE(50,150mg kg-1, ig ,d1 to d11l) could also enhance the low thymus index and the IL-2 production of splenocytes from HepA bearing mice treated by 5-Fu .Furthermore ,TAE could not only enhance ConA induced splenocytes proliferation and IL-2 production ,but also enhance the low TNF- a production of peritoneal macrophage of S180 tumor bearing mice treated by CTX. The experiments in vitro showed that TAE (25mg L-1) could enhance the proliferation response and IL-2 production of splenocytes induced by suboptional dose of ConA, it can also enhanceTNF- a production of peritoneal macrophages induced by suboptional dose of LPS from normal mice.These suggested that TAE could not only improve low immune function of normal and tumor-bearing mice,but also could enhance proliferation and/or secretion of two kinds of immunocytes(splenocytes , M s).3.Synergetic effect of TAE on antitumor effect of chemotherapeutic agentsIn combination with TAE(10 , 20 , and 40 mg kg-1 , ig ,d1 to d11) and CTX( 5, 10 ,and 20 mg kg-1,ip ,d1,4,7,10) or 5-Fu (5 ,10 and 20mg kg-1, ip ,d1,4,7,10) treated S180 or HepA tumor in mice, respectively. Data were analyzed with a software of the dynamics of drug interaction . Q values were all from -1 to 1 .This suggested that TAE had synergetic effect in combination with CTX or 5-Fu.4.Effect of TAE on the total leucocyte count in peripheral blood suppressed by CTXThe results showed that TAE(15,50 and 150mg kg-1 ,ig ,dl to dl 1) could amelionate the decreased blood leucocyte count induced by CTX(80mg kg-1 ,ip ,d6and d7) in normal mice. Furthermore, TAE(15 , 50 and 150mg kg-1 ,ig ,dl to dl 1) could amelionate the decreased blood leucocyte count induced by CTX(50mg kg-1 ,ip,d1,4,7,10) in S18... |
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