Abstract:Objective To study the 5-azacytidine’s demethylation for dickkopf-related protein 3 (DKK3) gene and its effects on SGC7901 gastric cancer cells’ proliferation and apoptosis. Methods SGC7901 gastric cancer cells were treated with 5-azacytidine, and other SGC7901 gastric cancer cells without 5-azacytidine treatment served as the controls. The changes of DKK3 gene promoter’s methylation and the differences in cell proliferation curve, cell proliferation and apoptosis were compared. Results DKK3 gene in SGC7901 gastric cancer cells showed methylation before 5-azacytidine treatment, but showed unmethylation after 5-azacytidine treatment, indicating that 5-azacytidine induced DKK3 gene promoter’s demethylation. The proportion of G0/G1 phase, proliferation index (PI) and apoptosis rate in SGC7901 gastric cancer cells after 5-azacytidine treatment were all significantly higher than those in SGC7901 gastric cancer cells before 5-azacytidine treatment (all P<0.05), whereas the S-phase and G2/M phase in SGC7901 gastric cancer cells after 5-azacytidine treatment were both significantly lower than those in SGC7901 gastric cancer cells before 5-azacytidine treatment (both P<0.05). Conclusions DKK3 may be an anti-oncogene. 5-azacytidine can demethylate DKK3 gene promoter’s methylation, which can promote SGC7901 gastric cancer cells’ apoptosis and inhibit their proliferation.
[1] Kang WS, Cho SB, Park JS, et al. Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer[J]. J Cancer Res Clin Oncol,2013,139(1):97-106. [2] Das DS, Wadhwa N, Kunj N, et al. Dickkopf homolog 3(DKK3) plays a crucial role upstream of WNT/beta-CATENIN signaling for Sertoli cell mediated regulation of spermatogenesis[J]. PLoS One,2013,8(5):e63603. [3] 崔丹,翟博,张明,等.Dkk3在肝细胞肝癌中的表达及其临床意义[J].肝胆外科杂志,2014,22(4):304-307. [4] Tao L, Huang G, Chen Y, et al. DNA methylation of DKK3 modulates docetaxel chemoresistance in human nonsmall cell lung cancer cell[J].Cancer Biother Radiopharm,2015,30(2):100-106. [5] Rukova B, Staneva R, Hadjidekova S, et al.Whole genome methylation analyses of schizophrenia patients before and after treatment[J].Biotechnol Biotechnol Equip,2014,28(3):518-524. [6] O'Donnell AH, Edwards JR, Rollins RA, et al. Methylation abnormalities in mammary carcinoma: the methylation suicide hypothesis[J].J Cancer Ther,2014,5(14):1311-1324. [7] 沈琼,陈陆俊,徐斌,等.组蛋白赖氨酸去甲基化酶1在食管癌中的表达及其意义[J].中华实验外科杂志,2015,32(5):1168-1170. [8] 孔繁静. DKK-3基因甲基化在胃癌病情及预后评估中的价值[J].检验医学与临床,2015,12(9):1253-1255. [9] 杨磊,贾彬,闫慧明,等.Dickkopf-3和血管内皮生长因子C在胃癌中的表达及临床意义[J].中国药物与临床,2015,15(3):351-353. [10] Medinger M, Muesser P, Girsberger S, et al. Dkk3 levels in patients with myeloproliferative neoplasms[J]. Thromb Res,2014,133(2):218-221. [11] Sood S,Srinivasan R. Alterations in gene promoter methylation and transcript expression induced by cisplatin in comparison to 5-Azacytidine in HeLa and SiHa cervical cancer cell lines[J]. Mol Cell Biochem,2015,404(1-2):181-191.