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抑制 Nanog 抑制了结肠直肠癌细胞的迁移,并增加了它们对氟尿嘧啶的敏感性。

Suppression of Nanog inhibited cell migration and increased the sensitivity of colorectal cancer cells to 5-fluorouracil.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

出版信息

Eur J Pharmacol. 2021 Mar 5;894:173871. doi: 10.1016/j.ejphar.2021.173871. Epub 2021 Jan 16.

Abstract

Nanog is a major transcription factor related to cellular multipotency that plays important roles in the development of tumor cells, drug resistance, migration, and stemness; indicating its great potential as a therapeutic target for various malignancies including colorectal cancer (CRC). Therefore, this study was aimed to evaluate the Nanog suppression effect using small interference RNA (siRNA) combined with 5-fluorouracil (5-FU) on CRC cells. Nanog-overexpressing SW-480 cells were transfected with Nanog si-RNA and treated with 5-FU, in combination or separately. Subsequently, it was observed that Nanog expression was significantly reduced after transfection of SW-480 cells using Nanog siRNA in mRNA and protein levels. Furthermore, Nanog knockdown significantly increased CRC cell sensitivity to 5-FU drug via modulating Bax and Bcl-2 mRNA expression. Also, Nanog knockdown and 5-FU treatment cooperatively decreased the migration and self-renewal ability of SW-480 cells by regulating the expression of relevant genes. Moreover, combination therapy led to cell cycle arrest at the sub-G1 phase in CRC cells. In conclusion, our results indicated that Nanog may play an important role in the drug sensitivity, migration, and self-renewal of CRC cells; suggesting Nanog as a promising target in combination with 5-FU for the development of new therapeutic approaches for CRC.

摘要

Nanog 是一种与细胞多能性相关的主要转录因子,在肿瘤细胞的发展、耐药性、迁移和干性中发挥重要作用;这表明它作为包括结直肠癌(CRC)在内的各种恶性肿瘤的治疗靶点具有巨大的潜力。因此,本研究旨在评估使用小干扰 RNA(siRNA)联合 5-氟尿嘧啶(5-FU)对 CRC 细胞的 Nanog 抑制作用。用 Nanog siRNA 转染过表达 Nanog 的 SW-480 细胞,并分别或联合用 5-FU 处理。随后,观察到在 SW-480 细胞中转染 Nanog siRNA 后,Nanog 在 mRNA 和蛋白水平上的表达明显降低。此外,Nanog 敲低通过调节 Bax 和 Bcl-2 mRNA 表达显著增加 CRC 细胞对 5-FU 药物的敏感性。同样,Nanog 敲低和 5-FU 治疗通过调节相关基因的表达,共同降低 SW-480 细胞的迁移和自我更新能力。此外,联合治疗导致 CRC 细胞的细胞周期在亚 G1 期停滞。总之,我们的结果表明,Nanog 可能在 CRC 细胞的药物敏感性、迁移和自我更新中发挥重要作用;表明 Nanog 作为一种有前途的靶点,与 5-FU 联合用于开发 CRC 的新治疗方法。

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