Molecular mechanisms of pancreatic cancer cells regulation by exosome derived from human bone marrow mesenchymal stem cells in vitro
10.3760/cma.j.cn113884-20230907-00062
- VernacularTitle:人骨髓间充质干细胞外泌体对胰腺癌细胞的影响及作用机制
- Author:
He ZHANG
1
;
Xiang LI
;
Beibei REN
;
Jing CHANG
;
Xin WANG
Author Information
1. 郑州大学附属肿瘤医院/河南省肿瘤医院病理科，郑州 450008
- Keywords:
Pancreatic neoplasms;
Bone marrow mesenchymal stem cells;
Exosomes;
Signaling pathway
- From:
Chinese Journal of Hepatobiliary Surgery
2024;30(5):375-380
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the molecular mechanism by which exosomes secreted from human bone marrow mesenchymal stem cells (BMSCs) regulate pancreatic cancer (PC) cells.Methods:The exosomes secreted by BMSCs were extracted and identified. Human PC cell lines (PANC-1 and AsPC-1) were then divided into 3 groups: simple cell group, exosome group and inhibitor group. For inhibitor group, PI3K/AKT Signaling Pathway inhibitor LY294002 was added, followed by exosomes. Subsequently, the protein expression of phosphatidylinositol 3-kinase (PI3K) protein kinase B(AKT) and their phosphorylated types was detected by Western-blot, and the contents of PC cell markers B7-H4 and CA199 were detected by ELISA kit. The CCK-8 experiment was mainly conducted to detect the proliferation ability of cells, the flow cytometry to detect apoptosis, and the Transwell experiment to detect the migration and invasion ability of cells.Results:The exosomes secreted by BMSCs were extracted successfully. The expression of PC cell markers B7-H4 and CA199, the proliferation rate, and the invasion and migration ability of cancer cells were all decreased for both PANC-1 and AsPC-1, while the apoptosis rate increased, all of which had statistical significance ( P<0.001). There were no significant differences for the above parameter in inhibitor group compared with the simple cell group ( P>0.05). The p-PI3K and p-Akt of PANC-1 cells in simple cell group were (5.81±1.87), (5.30±1.21), while up-regulated to (12.74±3.28), (11.22±2.35) with statistically significant differences ( P<0.001) after exosomes were added. Meanwhile, the above 2 kinds of protein expression of AsPC-1 cells in simple cell group were (4.75±0.87), (4.15±1.32), while increased to (10.83±3.19), (9.28±2.33) in exosome group with statistically significant differences ( P<0.001). On the other hand, there was no significant differences for the protein expression of P-PI3K and P-AKT in inhibitor group ( P>0.05) compared with the simple cell group. Conclusion:Exosomes secreted by BMSCS can inhibit the proliferation of PC cells and its migration and invasion ability by activating PI3K/AKT signaling pathway, thus playing a role in antitumor effect.
