关键词: 胰腺癌, 干扰素诱导的四肽重复蛋白 1, Wnt/β-catenin信号通路, 迁移, 侵袭

Abstract: Objective　To investigate the effect of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) on the progression of pancreatic cancer.Methods　The expression of IFIT1 in pancreatic cancer samples was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The mRNA levels of IFIT1 were detected by real-time quantitative PCR in pancreatic cancer cell lines (AsPC-1, MiaPaCa-2, BxPC-3, Patu8988, Panc-1, and CFPAC-1) and normal pancreatic cells. IFIT1 knockout cells were generated using the CRISPR/Cas9 system in AsPC-1 and BxPC-3 cells. AsPC-1 cells were divided into AsPC-1-ko-NC group (negative control group) and AsPC-1-ko-IFIT1 group (IFIT1 knockout group). Similarly, BxPC-3 cells were divided into BxPC-3-ko-NC group (negative control group) and BxPC-3-ko-IFIT1 group (IFIT1 knockout group). Cell viability was assessed using the cell counting kit-8 (CCK-8) assay in the four groups. Wound healing assay was performed to observe the closure status after 24 h and to evaluate cell migration ability in the four groups. Transwell assay was used to detect cell invasion ability in the four groups. The expression levels of IFIT1, β-catenin, and EMT-related proteins (E-cadherin, N-cadherin, Vimentin) in the four groups were detected by Western blot. Subsequently, the above four groups of cells were respectively injected subcutaneously into BALB/c nude mice, the volume and weight of the transplanted tumors were measured, and the expression of proliferation markers (Ki-67) in the transplanted tumors were measured. Results　Compared with normal tissues, the expression level of IFIT1 was significantly elevated in pancreatic cancer tissues. Following IFIT1 knockout in AsPC-1 and BxPC-3 cells, compared with the respective negative control groups (AsPC-1-ko-NC and BxPC-3-ko-NC groups), the AsPC-1-ko IFIT1 and BxPC-3-ko-IFIT1 groups exhibited decreased cell proliferation activity, migration, and invasion ability. In these knockout groups, E-cadherin protein expression was increased, while the expression of IFIT1, N-cadherin, Vimentin, and β-catenin was decreased. The in vivo xenograft tumor assay showed that compared with the negative control groups, the AsPC-1-ko-IFIT1 and BxPC-3-ko-IFIT1 groups had reduced tumor volume and weight, as well as decreased Ki-67 expression in the tumor tissues. Conclusion　IFIT1 promotes the proliferation, migration, invasion, and in vivo tumor growth of pancreatic cancer cells by activating the Wnt/β-catenin signaling pathway. EMT is regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Key words: pancreatic cancer, IFIT1, Wnt/β-catenin signaling pathway, migration, invade and attack