Zhang Lingmin,Wang Yaxu,Xie Kai,Zeng Linghai,Li Quan.Effect of 5-iodotubercidin on proliferation and apoptosis in human colon cancer HT-29 cells and demethylation of deleted in liver cancer-1 gene[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(02):106-110.
Zhang Lingmin,Wang Yaxu,Xie Kai,Zeng Linghai,Li Quan.Effect of 5-iodotubercidin on proliferation and apoptosis in human colon cancer HT-29 cells and demethylation of deleted in liver cancer-1 gene[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(02):106-110.DOI:
Effect of 5-iodotubercidin on proliferation and apoptosis in human colon cancer HT-29 cells and demethylation of deleted in liver cancer-1 gene
Objective To explore the effect of 5-iodotubercidin (ITU) on the proliferation and apopto
sis in human colon cancer HT-29 cells and on the expression of deleted in liver cancer-1 (DLC-1) gene. Methods HT-29 cells were treated with different concentrations of ITU (0.1
0.5
1
2
4
6
8
and 10 μmol/L) for 48 h
and the cell viability was studied by MTT assay. HT-29 cells were co-cultured with different concentrations of ITU (0
2
4
and 6 μmol/L) for 48 h
and the apoptosis rate was detected by flow cytometry. Meanwhile
the methylation levels of CpG islands at promoter region of DLC-1 gene were determined by bisulfite sequencing PCR (BSP). The DLC-1 mRNA expression levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and the DLC-1 protein expression levels were detected by Western blotting. Results ITU distinctly inhibited the proliferation of HT-29 cells in a concentration-dependent manner in a certain range
and the 6 μmol/L group had the greatest effect
with IC
50
of 5.92±0.62 μmol/L. The apoptotic rates of HT-29 cells treated with ITU (0
2
4
and 6 μmol/L) were (9.56±2.21)%
(22.18±3.16)%
(34.23±3.16)%
and (40.5±3.16)%
respectively
which were increased in a concentration-dependent manner. The methylation rates of CpG islands at the promoter region of DLC-1 gene were 91.67%
75.00%
61.67%
and 43.33%
respectively
after treatment with ITU (0
2
4
and 6 μmol/L). The results showed that ITU could decrease the methylation of DLC-1 gene promoter region. Little of DLC-1 mRNA and protein expression was detected in HT-29 cells
and ITU treatment increased the expression in a concentration-dependent manner. Conclusion ITU can inhibit the proliferation of HT-29 cells and induce apoptosis through decreasing the methylation level of DLC-1 gene promoter region and increasing the DLC-1 gene expression.