Department of Medical Biology, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey.
Med Oncol. 2022 May 23;39(5):98. doi: 10.1007/s12032-022-01688-x.
Anaplastic thyroid cancer cases with poor prognosis are associated with epigenetic modifications such as abnormal DNA methylation. Epigallocathesin-3-gallate (EGCG) is a polyphenol compound of green tea that is still under investigation on its role in cancer prevention. EGCG is known as an epigenetic diet in DNA methyltransferase inhibitor. The cytotoxic effects of Dabrafenib, EGCG, and dabrafenib in combination with EGCG were assessed by using WST-8 assay; and also, Flow cytometry was utilized to identify cells undergoing apoptosis after treatments of the SW-1736 cells. We investigated the mRNA expression of genes involved in epigenetic events in SW-1736 cells by real-time qRT-PCR following the treatments. We demonstrated for the first time that the Dabrafenib-EGCG combination reduced cell viability significantly depending on concentration and induced apoptosis by 8.49-fold through investigating the additive effect together on SW-1736 cells. The IC doses of Dabrafenib and EGCG for 48 h were determined as 6.7 μM and 22.5 μM, respectively. The results of qRT-PCR demonstrated that the Dabrafenib-EGCG combination significantly caused the down-regulation of genes involved in epigenetic regulation. We suggest that the combination of Dabrafenib and EGCG following in vivo phase studies will contribute as an alternative treatment option for the treatment of ATC.
预后不良的间变性甲状腺癌与表观遗传修饰有关，如异常的 DNA 甲基化。表没食子儿茶素没食子酸酯（EGCG）是绿茶中的一种多酚化合物，其在癌症预防中的作用仍在研究中。EGCG 是一种 DNA 甲基转移酶抑制剂的表观遗传饮食。通过 WST-8 测定法评估了达布拉非尼、EGCG 以及达布拉非尼与 EGCG 联合应用的细胞毒性作用；并利用流式细胞术鉴定 SW-1736 细胞经处理后发生凋亡的细胞。我们通过实时 qRT-PCR 研究了 SW-1736 细胞中涉及表观遗传事件的基因在经处理后的 mRNA 表达。我们首次证明，达布拉非尼-EGCG 联合治疗可显著降低细胞活力，这取决于浓度，并通过共同研究对 SW-1736 细胞诱导 8.49 倍的凋亡。达布拉非尼和 EGCG 的 IC 剂量在 48 小时分别为 6.7 μM 和 22.5 μM。qRT-PCR 的结果表明，达布拉非尼-EGCG 联合治疗可显著下调参与表观遗传调控的基因。我们建议，在体内研究阶段之后，将达布拉非尼与 EGCG 联合应用，将作为治疗 ATC 的替代治疗选择。
