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

被引:17
作者
Khosravi, Neda [1 ]
Shahgoli, Vahid Khaze [1 ,2 ]
Amini, Mohammad [1 ]
Safaei, Sahar [1 ]
Mokhtarzadeh, Ahad [1 ]
Mansoori, Behzad [1 ,2 ]
Derakhshani, Afshin [1 ]
Baghbanzadeh, Amir [1 ]
Baradaran, Behzad [1 ,3 ]
机构
[1] Tabriz Univ Med Sci, Immunol Res Ctr, Daneshghah Ave, Tabriz 5166614766, Iran
[2] Univ Southern Denmark, Inst Mol Med, Dept Canc & Inflammat Res, Odense, Denmark
[3] Tabriz Univ Med Sci, Fac Med, Dept Immunol, Tabriz, Iran
关键词
Colorectal cancer; siRNA; Nanog; 5-Fluorouracil; Chemosensitivity;
D O I
10.1016/j.ejphar.2021.173871
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Box and Bcl-2 mRNA expression. Also, Nanog knockdown and 5-FU treatment cooperatively decreased the migration and self-renewal ability of SW480 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.
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页数:9
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