Sanaei Masumeh, Kavoosi Fraidoon, Sahraeian Hamed
Research Center for Non-communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Fars Province, Iran.
Student of Research Committee, Jahrom University of Medical Sciences, Jahrom, Fars Province, Iran.
Int J Prev Med. 2021 Mar 29;12:33. doi: 10.4103/ijpvm.IJPVM_410_19. eCollection 2021.
Epigenetic changes, including DNA methylation and histone modification, alter gene expression without the nucleotide template alterations and are associated with all stages of tumor formation and progression. Previously, we investigated the effects of DNA demethylating agents and histone deacetylase inhibitors on hepatocellular carcinoma and colon cancers. The current study aimed to investigate the effects of 5-aza-2'-deoxycytidine (5-AZA-CdR, decitabine) and valproic acid (VPA), individually as well as combined on apoptosis induction and cell growth inhibition in colon cancer HT 29 cell line.
The effect of the compounds on the cell viability was measured by MTT assay. To determine cell apoptosis, the cells were treated with 5-aza-CdR and VPA. Propidium iodide was used for staining and the cells were analyzed using flow cytometry.
Both agents decreased cell viability in a time and dose-dependent manner significantly ( < 0.002). The results of flow cytometry demonstrated that 5-aza-CdR and VPA induced apoptosis significantly as opposed to control groups. Maximal percentage of apoptotic cells was obtained after 48 h with combined treatment.
Our findings suggest that 5-aza-CdR and VPA can significantly inhibit cell growth and induce apoptosis in colon cancer HT 29 cell line.
表观遗传变化,包括DNA甲基化和组蛋白修饰,在不改变核苷酸模板的情况下改变基因表达,并且与肿瘤形成和进展的各个阶段相关。此前,我们研究了DNA去甲基化剂和组蛋白脱乙酰酶抑制剂对肝细胞癌和结肠癌的影响。本研究旨在探讨5-氮杂-2'-脱氧胞苷(5-AZA-CdR,地西他滨)和丙戊酸(VPA)单独及联合应用对结肠癌HT 29细胞系凋亡诱导和细胞生长抑制的影响。
通过MTT法检测化合物对细胞活力的影响。为了确定细胞凋亡情况,用5-氮杂-2'-脱氧胞苷和丙戊酸处理细胞。使用碘化丙啶进行染色,并通过流式细胞术分析细胞。
两种药物均以时间和剂量依赖性方式显著降低细胞活力(<0.002)。流式细胞术结果表明,与对照组相比,5-氮杂-2'-脱氧胞苷和丙戊酸显著诱导细胞凋亡。联合处理48小时后获得最大凋亡细胞百分比。
我们的研究结果表明,5-氮杂-2'-脱氧胞苷和丙戊酸可显著抑制结肠癌HT 29细胞系的细胞生长并诱导细胞凋亡。