Kalantar Hadi, Rashidi Mohsen, Kalantar Mojtaba, Tavallaei Mahmoud, Hosseini Sayed Mostafa
Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Iran J Pharm Res. 2021 Winter;20(1):133-140. doi: 10.22037/ijpr.2019.111945.13442.
Epigenetic mechanisms are the most important factors contributing to both the development and metastasis of cancer cells. We aimed to scrutinize the role of epigenetic alternations of genes involved in cancer metastasis, including (metastasis indicator) and (a novel tumor suppressor), in the A549 lung cancer cell line. The A549 cells were cultured in the DMEM medium. Valproic acid (VPA) was used as a histone deacetylase inhibitor. Caspase-3 activity was assessed by adding DEVD-pNA substrate to the cell lysate. Gene expression was determined by real-time PCR. Finally, protein expression was assessed by western blot. The results showed that VA significantly decreased the expression of the gene and its protein level. This was further accompanied by lower expressions of and genes. On the other hand, the expression of and its protein were significantly increased in the cells accompanied by higher activity of caspase-3 ( 0.05). Our results showed that epigenetic regulation of , , and might be involved in the pathogenesis and metastasis of lung cancer. Therefore, the use of histone deacetylase inhibitors can be effective in the suppression of metastases and the treatment of these tumors.
表观遗传机制是导致癌细胞发展和转移的最重要因素。我们旨在研究参与癌症转移的基因（包括转移指标和一种新型肿瘤抑制因子）的表观遗传改变在A549肺癌细胞系中的作用。将A549细胞培养于DMEM培养基中。丙戊酸（VPA）用作组蛋白脱乙酰酶抑制剂。通过向细胞裂解物中添加DEVD-pNA底物来评估半胱天冬酶-3的活性。通过实时PCR测定基因表达。最后，通过蛋白质印迹法评估蛋白质表达。结果表明，VPA显著降低了基因的表达及其蛋白质水平。这进一步伴随着和基因表达的降低。另一方面，在细胞中，的表达及其蛋白质显著增加，同时半胱天冬酶-3的活性更高（P<0.05）。我们的结果表明，、、和的表观遗传调控可能参与肺癌的发病机制和转移。因此，使用组蛋白脱乙酰酶抑制剂可能有效抑制转移并治疗这些肿瘤。
