T-cadherin Expression Induced By 5-Aza-2'-deoxycytidine In HepG2-derived Tumors In Nude Mice And Its Inhibitory Effects On Tumor Growth

AIM: This study was to observe whether the demethylation agent 5-Aza-2'–deoxycytidine ( 5-Aza-CdR) can induce the HepG2 cell to express T-cadherin gene, and inhibit the proliferation of the cancer cells in nude mice.METHODS : The HepG2-derived tumor model in nude mice was generated by subcutaneous inoculation of HepG2 cells. 21 Nude mice were randomly divided into two groups, the experiment group with 11 mice (5-Aza-CdR group) and the control group with 10 mice. The mice of the experiment group were given 5-Aza-CdR at 1mg/kg(in 200μl PBS) by intraperitoneal injection, three times per week( at an interval of 2-3 days) for 4 weeks, and the mice of the control group were only given the same volume of PBS. The mice were then sacrificed at the end of the fourth week. The tumor growth in nude mice was observed,and the T-cadherin mRNA and protein expressions of the tumors were detected by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry.RESULTS: At the end of the fourth week, the T-cadherin mRNA expression in the tumors of the experiment group was significantly higher than that in the tumors of the control group (t=6.613, P<0.05); Immunohistochemistry further showed that the protein expression of T-cadherin in the HepG2-derived tumor cells of the control group was not found, however, the T-cadherin expression appeared on the membranes of the HepG2-derived tumor cells of the experiment group. After 4 weeks treatment with 5-Aza-CdR, the average volume of HepG2-derived tumors in the experiment group was significantly smaller than that in the control group(1005.78±419.69 vs 1423.78±645.54mm3 ) , there was a significant difference in tumor volume between the two groups(t=2.337,P=0.025<0.05).CONCLUSION:5-Aza-CdR induces HepG2 cells to re-express T-cadherin, and inhibits the growth of HepG2-derived tumors in nude mice. The mechanism may correlate with the demethylation of the methylated T-cadherin promoter induced by 5-Aza-CdR,and the T-cadherin reexpression inhibits the growth of the HepG2-derived tumors in nude mice.