Secer Celik Fatma, Eroglu Gunes Canan, Kurar Ercan
Department of Medical Biology and Genetics, Faculty of Medicine, Ankara Medipol University, Ankara, Turkey.
Department of Medical Biology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.
Int J Mol Cell Med. 2023;12(3):220-228. doi: 10.22088/IJMCM.BUMS.12.3.220.
Endometrial carcinoma is one of the most common types of cancer among women. The progression of cancer occurs via the Epithelial- Mesenchymal Transition (EMT) pathway. Cells lose their epithelial properties and become mobile. For this reason, the EMT process is one of the most important step to be targeted in cancer treatment. Oleandrin is a cardiac glycoside and its use is limited due to its narrow therapeutic index. In this study, we aimed to evaluate effects of lower level Oleandrin doses on EMT process in endometrial carcinoma. Oleandrin was administrated to Ishikawa endometrial adenocarcinoma cells at different doses and times. IC dose was determined by XTT proliferation test. Expression analysis of EMT-related genes was then performed by qRT-PCR. Invasion and colony formation abilities of cells were examined microscopically. Finally, the migration analysis of cancer cells was determined by the Wound Healing Assay. The IC dose of Oleandrin applied to Ishikawa cells was determined as 75.3 nM at the 48 h. According to qRT-PCR analysis, expression levels of ZEB1, FN1, ITGB1, VIM, SMAD2, SNAI1, SNAI2, SNAI3, and TGFB3 genes significantly decreased, but TIMP2, TIMP3, ITGAV and GSK3B genes significantly increased. In addition, Oleandrin significantly reduced colony formation and invasion of Ishikawa cells. According to the Wound Healing analysis, the migratory abilities of the Oleandrin-treated cells were reduced compared to the control. Low dose Oleandrin suppresses the EMT pathway in Ishikawa cells. It has been shown that Oleandrin significantly suppresses the cell's colony formation, invasion and migration ability both in gene expression analyzes and microscopically.
子宫内膜癌是女性中最常见的癌症类型之一。癌症的进展通过上皮-间质转化（EMT）途径发生。细胞失去其上皮特性并变得具有移动性。因此，EMT过程是癌症治疗中最重要的靶向步骤之一。夹竹桃苷是一种强心苷，由于其治疗指数狭窄，其应用受到限制。在本研究中，我们旨在评估较低剂量夹竹桃苷对子宫内膜癌EMT过程的影响。以不同剂量和时间将夹竹桃苷施用于 Ishikawa 子宫内膜腺癌细胞。通过XTT增殖试验确定IC剂量。然后通过qRT-PCR进行EMT相关基因的表达分析。通过显微镜检查细胞的侵袭和集落形成能力。最后，通过伤口愈合试验确定癌细胞的迁移分析。在48小时时，应用于Ishikawa细胞的夹竹桃苷的IC剂量确定为75.3 nM。根据qRT-PCR分析，ZEB1、FN1、ITGB1、VIM、SMAD2、SNAI1、SNAI2、SNAI3和TGFB3基因的表达水平显著降低，但TIMP2、TIMP3、ITGAV和GSK3B基因显著增加。此外，夹竹桃苷显著减少了Ishikawa细胞的集落形成和侵袭。根据伤口愈合分析，与对照相比，夹竹桃苷处理的细胞的迁移能力降低。低剂量夹竹桃苷抑制Ishikawa细胞中的EMT途径。已经表明，夹竹桃苷在基因表达分析和显微镜下均显著抑制细胞的集落形成、侵袭和迁移能力。
