目的：探讨Notch4调控活化转录因子2（activating transcription factor 2，ATF2）对胰腺癌（pancreatic cancer, PC）细胞侵 袭和迁移的影响及其可能的机制。方法：收集台州学院附属医院2015年2月至2019年7月手术切除的PC组织及其配对的癌旁 组织标本各60份，采用免疫组织化学技术检测Notch4的表达水平。采用siRNA技术敲减PC细胞系MiaPaCa-2和PANC-1中 Notch4基因的表达，Transwell法分析Notch4敲减对细胞侵袭及迁移的影响，qPCR及Western blotting法检测Notch4敲减对细胞 中Notch4和ATF2的mRNA及蛋白表达的影响。结果：与癌旁组织相比，Notch4在PC组织中的表达显著增加（P<0.01）。转染 Notch4 siRNA后，MiaPaCa-2和PANC-1中Notch4和ATF2 mRNA及蛋白表达水平显著下降（均P<0.01）。与Control siRNA组比 较，Notch4 siRNA组的PC细胞迁移和侵袭能力显著降低（均P<0.01）。结论：Notch4在PC组织中呈高表达，敲减Notch4可在转 录水平下调ATF2的表达，进而抑制PC细胞的侵袭及迁移能力。

Objective: To investigate the effect of Notch4 regulatingATF2 (activating transcription factor 2) on the invasion and migration of pancreatic cancer (PC) cells and its possible mechanism. Methods:Atotal of 60 pairs of PC tissues and corresponding para-cancerous tissues that surgically resected at Taizhou University Hospital during February 2015 and July 2019 were collected for this study. The expression of Notch4 was detected by immunohistochemistry. siRNA technology was used to knock down Notch4 gene expression in PC cell lines (MiaPaCa-2 and PANC-1). Transwell assay was used to analyze the effect of Notch4 knockdown on cell invasion and migration. qPCR and Western blotting (WB) were used to detect the effects of Notch4 knockdown on mRNA and protein expressions of Notch4 and ATF2. Results: Compared with para-cancerous tissues, the expression of Notch4 in PC tissues significantly higher (P<0.01). After Notch4 siRNA transfection, the mRNA and protein expressions of Notch4 and ATF2 in MiaPaCa-2 and PANC-1 cells significantly decreased (all P<0.01). Compared with Control siRNA group, the migration and invasion ability of PC cells in Notch4 siRNA groupsignificantlyreduced(allP<0.01).Conclusion:Notch4ishighlyexpressedinPCtissues.Knockdown of Notch4 can down-regulate the expression ofATF2 at the transcriptional level, thereby inhibiting the invasion and migration ability of PC cells.

浙江省医药卫生科技计资助（No. 2019RC314）；浙江省自然科学基金项目资助（No.LY16H160033）；国家级大学生创新创业训练计 划 资 助 项 目（No. 201910350008）