Dipeptidylpeptidase-4 inhibitor anagliptin inhibiting the formation and mechanism of lung metastasis in colorectal cancer
10.16098/j.issn.0529-1356.2024.05.009
- VernacularTitle:二肽基肽酶-4抑制剂阿拉格列汀抑制结直肠癌肺转移瘤的形成及其机制
- Author:
Yue LI
1
;
Si-Meng WEI
;
Xin WU
;
Xiao LIU
;
Qi LI
;
Chang CHEN
Author Information
1. 哈尔滨医科大学药学院药理学教研室,哈尔滨 150086
- Keywords:
Anagliptin;
Lung metastasis;
superoxide dismutase 1;
Reactive oxygen species;
Colorectal cancer;
Western blotting;
Mouse
- From:
Acta Anatomica Sinica
2024;55(5):582-588
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the formation and mechanism of dipeptidylpeptidase-4 inhibitor anagliptin inhibiting lung metastasis of colorectal cancer.Methods Twenty-four male BALB/c mice were randomly divided into normal group,model group,anagliptin group.The control group did not undergo any treatment.The model group was injected with 0.1 ml CT-26 cells of 109 cells/L.once through the tail vein of the mouse to construct a lung metastasis model,while the anagliptin group was injected intraperitoneally 20 mg/(kg d)0 day after constructing a lung metastasis model.The mice were sacrificed after 14 days.HE staining was used to detect the morphological alteration.Determination of CT-26 cell viability through MTT assay and CT-26 cell apoptosis was detected by flow cytometry and live/dead cell staining.Reactive oxygen species(ROS)production was measured by ROS kit.Western blotting was conducted to measure the expression level of Bcl-2,Bax,cleaved-caspase-3,superoxide dismutase(SOD-1)and SOD-2.Results HE staining showed that the administration of anagliptin could significantly inhibit the abnormal changes in the model group.Anagliptin inhibited the viability of CT-26 cells above 2 mmol/L.Anagliptin promoted the apoptosis of CT-26 cells.Incubation of anagliptin in CT-26 cells significant promoted the production of ROS.Incubation of anagliptin stimulated the expressions of Bax and cleaved-Caspase-3,while down-regulated the expression of Bcl-2 in CT-26 cells.Administration of anagliptin decreased the expression of SOD-1,but not SOD-2.Conclusion Anagliptin promotes apoptosis of colorectal cancer cells and inhibits the formation of lung metastatic tumors through the SOD-1/ROS pathway.
