The inhibitory effects of antisense mTR and cisplatin on transplantable lung carcinoma in mice

Objective: To determine the inhibitory effects of cisplantin and sulfur-modified antisense oligodexyribonucleotide(ASODN) on the growth of transplantable lung carcinoma in mice and on the telomerase activity of carcinoma,liver and testis.Methods: Lewis lung glandular carcinoma cells(1×10P>7P>/ml) were inoculated subcutaneously to 44 C57 male mice.They were randomized into 6 groups.From the 10th day on,0.5 ml 0.9%NS and antisense mTR were intraperitoneally given to group Ⅰ and groupⅡ,respectively,every day for 6 days;0.5 ml DDP of different concentration,1.0 mg/kg,2.0 mg/kg and 4.0 mg/kg,were intraperitoneally injected on the 15th day once in Ⅲ, Ⅳ and Ⅴ groups,respectively;DDP and ASODN combined were applied to group Ⅵ.The telomerase activities of tumor,liver and testis were determined sermi-quantatativly by TRAP-ELASA.Results: Volumes of mice transplantable carcinoma in groups Ⅴ and Ⅵ were greatly reduced(P<0.01) comparing with other groups.The telomerase activity of mice carcinoma in groups Ⅴ and Ⅵ was the lowest(P<0.01) in contrast to other groups.Mice liver and testis telomerase activity in groups Ⅳ,Ⅴand Ⅵ presented significant reduction(P<0.05-P<0.01) in contrast to health control group and groupⅠ.In addition,the liver and testis telomerase activity of group Ⅱ showed no significant reduction(P>0.05) in contrast to groupⅠand healthy contrast group.Conclusions: ASODN alone have no effects on tumor growth and liver and testis telomerase activity,but has inhibitory effect on the telomerase activity of transplantable lung carcinoma.Treatment with DDP alone or in combination with ASODN and DDP demonstrates apparent carcinoma volume shrinkage,carcinoma necrosis and telomerase activity inhibition.Combination of DDP and ASODN has cooperative effect on transplantable lung carcinoma.