Effect Of β-Carboline Derivatives HMD On The Growth Of Subcutaneous Transplant Human Hepatocellular Carcinoma In BALB/c Nude Mice

Objective: To investigate the effect of β carboline derivatives (HMD) on growth of subcutaneoustransplant hepatocellular carcinoma in BALB/c nude mice. Methods:(1).To observe reproductive capacityof BALB/c nude mice in IVC cages and barrier breeding facilities.30male BALB/c mice(nu/nu)and40BALB/c female mice(nu/+)were observed and statistically classified according to the data of the breedingcards.(2).To observe the acute toxicity of HMD in mice by iv injection, and to determine the LD50.TheLD100in mice by iv injection was preliminarily measured to be25mg/kg,then KM mice were divided into7groups randomly; the interval between groups was set according to1:0.8.Bliss＇S method was used to testthe LD50of HMD in KM mice by iv injection.(3).To establish a subcutaneous tumor model in BALB/cnude mice by using human hepatocellular carcinoma cell line HepG2and observe its biologicalcharacteristics.HepG2cell line was cultured and the cultured cells were divided into four cell suspensiongroups(group1:5×10~7cells/ml,n=10;group2:2×10~7cells/ml,n=10;group3:1×10~7cells/ml,n=10;group4:1×10~6cells/ml,n=10).Each of40mice was injected0.2ml HepG2cell suspension subcutaneously intoarmpit. Feeding and activity status of tumor bearing mice, formation time, ingestion, psychosis, growth andsize of the tumor were observed.(4).To study the effect and toxicity of HMD on the growth of humanhepatocellular carcinoma cell line (HepG2) xenograft tumor in nude mice. A tumor model of human HCCwas created by subcutaneous inoculation of2×10~7(cells/ml,0.2ml) HepG2cells into BALB/c male nudemice. The mice were randomized to low-(0.22mg/kg),medium-(0.44mg/kg),and high-dose HMD(0.87mg/kg)group, saline group and5-Fu group. The mice in each group received iv injection of the drug for15days. The effects of HMD on the growth of human hepatocellular carcinoma, the weight and pathologicalchanges of nude mice＇S main organs were observed. Results:(1).The pregnant rates of BALB/c nudemice Was80%. The differences in reproduction performance of BALB/c nude mice were not significant inIVC cages and barrier breeding facilities(P>0.05). The nu/nu homozygous offspring weaning rate was thebest at the group of2♀(nu/+) and1♂(nu/nu) crossbreeding in IVC cages.(2).LD50of HMD in KM mice byiv injection is10.896mg/kg, with a95%confidence limit of9.5568~12.525mg/kg.(3).The subcutaneouslytumor model of human hepatocellular carcinoma with nude mice has been established. The overall tumorformation rate was100%,and the average tumor appearing time was3~7days after tumor cell suspensioninjection.(4).Compared with saline group, the mice in HMD groups and5-Fu group showed significantinhibition in the growth of the transplanted tumor(P<0.01).The inhibitory rate of HMD to the mouse weight.Compared to the saline group, the inhibitory effects of HMD(0.44,0.87mg/kg)were of statisticsignificance(P<0.01).Contrast to the negative control, there were no significant difference to the weight ofkidney and kidney index in HMD groups and5-Fu group, but there were significant statistically in theweight of liver and liver index (P<0.05). Conclusion:(1).The BALB/c nude mice sub-skin modeltransplanted with human liver cancer is constructed successfully.(2).HMD could exhibit an inhibitory effecton the growth of transplanted HepG2tumor, and the mice don’t appearance toxicity function.