The Inhibitory Effects Of TSLC1 Overexpression On Nude Mice Xenograft Tumor Of Bladder Cancer

Objective:To explore the effects of TSLC1 overexpress on nude mice xenograft tumor of bladder cancer, and investigate the related molecular mechanisms.Methods:3 groups of nude mice, respectively, were subcutaneously implanted 1*107/ml T24 TSLC1 overexpression cells(Ad-TSLC1-T24) and T24 overexpression control cells(Ad-T24) and T24 cells.Test the tumor volume every 5 days to draw the tumor growth-curve of tumor volume according time in every groups. 5weeks later,the nude mices were killed.The tumor volume and weight were recorded and calculated the abti-tumor rate.The pathology changes of carcinoma were observed after HE staining by light microscope.TSLC1 expression in xenografts in nude mice was measured by RT-PCR,western blot and immunohistochemistry.The expression of Bcl-2,Bax and Caspase-3 mRNA were detected by RT-PCR. And the expression of Bcl-2,Bax and Caspase-3 protein were detected by Western Blot.Results:Three groups of nude mice model was successfully constructed. The tumor growth curves showed that the tumor growth was slow in the Ad-TSLC1-T24 group(p<0.05). The volume and weight of tumor in Ad-TSLC1-T24 group after 5 weeks were significantly low than control groups(P<0.05).The anti-tumor rate in Ad-TSLC1-T24 group was significantly higher than Ad-T24 group(47.6% VS 14%,P<0.05).In Ad-TSLC1-T24 group the tumor cells showed apoptotic changes such as karyopyknosis and nuckear fragmentation under light microscope.Immunohistochemistry analysis and RT-PCR and western blot found TSLC1 decreased expresson in Ad-T24 group and T24 group,and up regulation in Ad-TSLC1-T24 group. RT-PCR showed that the mRNA expression of Bax and Caspase-3 significantly higher in Ad-TSLC1-T24 group than in two control groups(P<0.05), and Bcl-2 mRNA in Ad-TSLC1-T24 group were obvious decreased(P<0.05). The Western Blot showed that the protein expression of Bax and Caspase-3 was obviously increased in Ad-TSLC1-T24 group compared with twocontrol groups(P<0.05).Meanwhile,the expression of Bcl-2 in Ad-TSLC1-T24 group were obvious decreased(P<0.05).Conclusion:1.TSLC1 overexpression would inhibited the growth of xenografted human bladder cancer cell in nude mice.2.TSLC1 overexpression up-regulated Caspase-3 expression and increase the Bax/Bcl-2 expression, induced the tumor cells apoptosis.