Notch4 inhibition reduces migration and invasion and enhances sensitivity to docetaxel by inhibiting Akt/fascin in pancreatic cancer cells

Notch4 抑制通过抑制胰腺癌细胞中的 Akt/fascin 来减少迁移和侵袭并增强对多西他赛的敏感性

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作者:Cui-Juan Qian, Yi-Yi Chen, Xin Zhang, Fu-Qiang Liu, Ting-Ting Yue, Bei Ye, Jun Yao

Abstract

Overexpression of Notch4 is associated with a variety of tumor types. Only sparse information exists on Notch4 expression in pancreatic cancer (PC). The present study demonstrated that Notch4 expression was significantly upregulated in PC cell lines compared with a non-transformed pancreatic epithelial cell line, HPDE6c-7. To investigate the possible role of Notch4 in PC cells, an RNA interference approach was used to silence Notch4 expression. The results revealed that small interfering RNA (siRNA) targeting Notch4 significantly impeded the viability, migration and invasion abilities of PC cells in vitro. Downregulation of Notch4 with siRNA sensitized cells to the action of docetaxel. Furthermore, Notch4 downregulation enhanced the inhibition of Akt activation and the fascin expression induced by docetaxel in PC cells. Together, these data provide insight into the function of Notch4 and suggest that Notch4 may represent a new potential target for gene therapy in PC.

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