The therapeutic effects of survivin antisense nucleic acid combined with paclitaxel on subcutaneous xenograft mouse model of Balb/c / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the therapeutic effects of combined application of survivin antisense nucleic acid and taxol in subcutaneous xenograft mouse model of Balb/c and to preliminarily investigate the mechanism of the anticancer effects.Methods The model of subcutaneous tumor was established by hypodermic injection of C26 cells into Bal b/c mice.The mice were then randomly divided into five groups through the internal tumor injectionthe blank group (C),lipo2000 group (L),paclitaxel group (T),survivin antisense nucleic acid group (A),and survivin antisense nucleic acid combined with paclitaxel group (A+T).We observed tumor growth,determined cell apoptosis by TUNEL method,and detected the expression of survivin by Western blot.Results ① All treatment groups had T/C<60%,which was significantly different from that of group L (P <0.05);the intervention was proved effective in vivo .The tumor inhibition rate of mice tumor weight showed that there were significantly curative effects in groups T,A and A+ T compared with that in group C (P < 0.05 ).The antitumor activity of paclitaxel (tumor inhibition rate of 21.82%±0.84%)could be improved by more than 59% through combination therapy (tumor inhibition rate of 54.1 6% ± 0.32%)concerning inhibition of tumor weight growth.② TUNEL method detected apoptotic cellsThe tumor cells hardly had apoptosis in the blank group while T group and A group had a certain number of apoptotic cells.The experiment results suggested that PTX could promote tumor cell apoptosis,and that not only A+T strengthened the effect in killing tumor cells,but also the synergy of both could influence tumor resistance and ultimately make the effect in promoting tumor cell apoptosis conspicuous.③ The expression of survivin proteinThe results showed that the expression of survivin protein in group A + T was obviously decreased without the expression of β-actin affected;it did not change significantly in group C compared with group L.The ratio of the A-value in groups T,A and A+T was 0.895 ±0.01 1,0.704 ±0.121 and 0.345 ± 0.01 9,respectively.Analysis of variance t-test showed that the expression level in group A+T obviously differed from that in groups C,L,A and T (P <0.05).Conclusion The combined therapy of survivin antisense nucleic acid and taxol can promote tumor cell apoptosis by downregulating the expression of survivin protein,reduce the body’s resistance to drugs and create synergetic effects.