The Therapeutic Effect Of ACT001 On Mice Bearing Ascitic Hepatoma 22

OBJECTIVE: To investigate the therapeutic effect of ACT001 on peritoneal effusion in mice with ascites tumor model.Methods: H22 ascites mouse model was established by i.p.injecting 56 BALB/C mice with H22 cells(0.2ml,about2×107 cells).24 h inoculation of mice Mice were then divided randomly into ACT001,DDP,MCL combined with DDP and control,once a day for 7 days and 10 of each group.The bodyweights,abdomen circumference and behavior of the mice were measured everyday before treatment and then draw the weight and abdomen curve.After 24 h of the last administration,the expression of AMPK,Caspase-3,and RIP-3 in each group were detected by Western blot on peritoneal effusion in mice with ascites tumor,and the effect of drug on apoptosis of ascites cells that extracted in ascites were detected by Flow cytometry.After 24 h of the last administration,the effect of the drug on the mouse blood tumor markers,which were taken from the orbital blood that from the mice were sacrificed.The histomorphology and cell morphology of ascites and liver tissues were detected by hematoxylin-eosin staining.To observe the overall survival time of transplanted miceRESULTS: 1.ACT001 can inhibit the body weight and ascites formation.(P<0.05)2.ACT001 can enhance the sensitivity of cisplatin in the treatment of H22 ascites tumor model bearing mice.(P<0.05).3.Flow cytometry showed that ACT001 could promote the apoptosis of H22 cells.(P<0.05)4.Compared with the control group,ACT001 could decrease the levels of AFP in the blood tumor markers.(P<0.01).but had no significant effect on CEA,CA199 and CA242(P<0.05).5.The AMPK and RIP-3 expression level was not high in four groups.(P>0.05).The Caspase-3 expression level was higher than control groups,and which was lower than ACT001 combined with DDP group.(P<0.05).6.The liver edema and lymphocyte infiltrationin in control group was very serious than experiment group.Compared with the experimental group,Lobular diffuse edema of the liver cells andcytoplasm loose in control group.(P<0.05).7.Compared with the control group,combined group can prolong the overall survival time.(P<0.05).CONCLUSION: ACT001 can effectively inhibit the formation of ascites in H22 mice.Meanwhile ACT001 can enhance the sensitivity of cisplatin in the treatment of H22 ascites tumor model bearing mice.The mechanism may be according to the Caspase-3 overexpression and increased tumor cell apoptosis.