The roles of MDM2 in mediating the inhibitory effects of dihydroartemisinin on proliferation and migration of lung adenocarcinoma cells
10.19405/j.cnki.issn1000-1492.2025.12.015
- VernacularTitle:MDM2 在双氢青蒿素抑制肺腺癌细胞增殖和迁移中的作用
- Author:
Huijuan Ling
1
;
Yu Liu
1
;
Yayu Zhu
1
;
Ke Niu
1
;
Jing Tang
1
;
Liwen Chen
2
Author Information
1. Dept of Clinical Laboratory Diagnostics , The Second Clinical Medical College of Anhui Medical University, Hefei 230601
2. Dept of Clinical Laboratory Diagnostics , The Second Clinical Medical College of Anhui Medical University, Hefei 230601; Dept of Blood Transfusion , The Second Afiliated Hospital of Anhui Medical University, Hefei 230601
- Publication Type:Journal Article
- Keywords:
lung adenocarcinoma;
MDM2;
dihydroartemisinin;
proliferation;
migration;
epithelial-mesenchymal transition
- From:
Acta Universitatis Medicinalis Anhui
2025;60(12):2316-2325
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of murine double minute 2(MDM2) in dihydroartemisinin′s(DHA) inhibition of lung adenocarcinoma cell proliferation and migration.
Methods:CCK8 assay was used to detect the inhibitory effect of gradient concentrations of DHA(0, 5, 10, 25, 50 and 100 μmol/L) and time gradients(0, 24, 48, and 72 h) on the proliferation of lung adenocarcinoma A549 and PC9 cells, and the half maximal inhibitory concentrate(IC50) were calculated respectively. Colony formation and scratch assays were used to detect the inhibitory effects of DHA on colony formation and migration of A549 and PC9 cells. Western blot was used to detect the inhibitory effects of DHA on MDM2 expression and epithelial-mesenchymal transition(EMT)-related proteins E-cadherin and N-cadherin. The promoting effects of MDM2 on proliferation, migration and EMT of lung adenocarcinoma cells were verified by small interfering RNA-mediated knockdown of MDM2(si-MDM2). The reversal effects of MDM2 overexpression on DHA′s inhibition on the proliferation and migration of A549 and PC9 cells were observed.
Results:DHA inhibited the proliferation of A549 and PC9 cells in a dose⁃ and time⁃dependent manner,with IC50 values of 30. 57 and 78. 61 μmol/L , respectively. Compared with the Control group , A549 and PC9 cells had significantly decreased colony formation (both P < 0. 01) and migration (both P < 0. 01) upon treatment with DHA. Moreover, DHA significantly inhibited the protein expression levels of MDM2 and N ⁃cadherin in A549 and PC9 cells , and upregulated the expression of E ⁃cadherin protein (both P < 0. 05) . Compared with si⁃Control ,si⁃MDM2 significantly inhibited the protein levels of MDM2 and N ⁃cadherin in A549 and PC9 cells , and upregulat⁃(both P < 0. 01) of both cells. After overexpression of MDM2 in A549 and PC9 cells , the proliferation and migra⁃ tion ability were significantly enhanced (both P < 0. 05) , and the inhibitory effects of DHA were partially reversed by MDM2 overexpression (both P < 0. 05) .
Conclusion:DHA effectively inhibits the proliferation and migration of lung adenocarcinoma cells , and its mechanism is associated with the suppression of MDM2.
- Full text:2026030323141811942MDM2在双氢青蒿素抑制肺腺癌细胞增殖和迁移中的作用_凌惠娟.pdf
