Abstract:

Abstract:Objective To investigate the inhibitory effect of antisense oligonucleotides (ASON) of telomerase on the growth of bladder cancer in vivo of nude mice and to confirm its therapeutic effect on bladder cancer.Methods Bladder carcinoma EJ cells cultured with medium and thiophosphoric acid-modfied ASON PS-ASON were inoculated into BALB/c mice as control group(n=24) and PS-ASON treatment group(n=12).The rates  of tumor genesis were observed in two groups.The mice in control group were divided into three groups(n=8)  depending on the different medicines fed to the mice as soon as 20 mm tumor formed.The mice in blank control group, PS-ASON  injection  group and chemotherapy medicine group were injected with saine,PS-ASON,and pharmorubicin,respectively.The tumor growth,weight of nude mice,tumor volumes and the survival rate were measured and observed.Then  the morphological changes of tumor tissue were observed  under light microscope.Results The rate of tumorgenesis of the mice in PS-ASON treatment group was lower than that in control group (P<0.01),the time of tumorgenesis in PS-ASON treatment group was more than that in control group (P<0.01) and the weight of the mice in treatment group was heavier than that in control group (P<0.01).After the mice were treated for 12 d,the tumor volumes of the mice in PS-ASON injection group and pharmorubicin  group were smaller than that in blank control group (P<0.01),but there was no significant difference in tumor volume between PS-ASON injection  group and pharmorubicin  group(P>0.05).The weight of the mice in blank control group lost obviously;the weight of the mice in PS-ASON injection group was bigger than that in blank control group(P<0.01) 16 d after inoculation.The weight of the mice in pharmorubicin  group were lower than that in PS-ASON injection  group(P<0.01) 8 d after inoculation;but there was no significant difference in the weight of the mice between blank control group and pharmorubicin  group(P>0.05).Necrosis and apoptosis of incubating tumor cells were observed in  PS-ASON injection  group and pharmorubicin group under light microscope.The survival rate of the nude mice in PS-ASON  group was higher than those in blank  group (P<0.001) and pharmorubicin  group(P<0.01).Conclusion ASON of telomerase inhibit the  growth of bladder cancer significantly in vivo.Its therapeutic efficacy is similar to the chemotherapy medicine,and it can be used for the further research on therapy for bladder cancer.

Key words: bladder neoplasms, telomerase, antisenseoligo nucleotides, in vivo experiment