Matrine inhibits proliferation and promotes autophagy and apoptosis in non-small cell lung cancer cells by deactivating PI3K/AKT/mTOR pathway.
10.12122/j.issn.1673-4254.2019.07.02
- Author:
Yanmei HAO
1
;
Hongmei YIN
2
;
Chaomang ZHU
2
;
Feng LI
2
;
Yingjie ZHANG
1
;
Yuyun LI
1
;
Xiaojing WANG
3
;
Duojie LI
2
Author Information
1. Department of Clinical Laboratory, Bengbu Medical College, Bengbu 233030, China.
2. Department of Radiotherapy, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
3. Anhui Clinical and Preclinical Key laboratory of Respiratory Disease, Bengbu Medical College, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
AKT pathway;
apoptosis;
autophagy;
matrine;
non-small cell lung cancer
- MeSH:
Alkaloids;
Apoptosis;
Autophagy;
Carcinoma, Non-Small-Cell Lung;
Cell Proliferation;
Humans;
Lung Neoplasms;
Phosphatidylinositol 3-Kinases;
Proto-Oncogene Proteins c-akt;
Quinolizines;
Signal Transduction;
TOR Serine-Threonine Kinases
- From:
Journal of Southern Medical University
2019;39(7):760-765
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the inhibitory effect of matrine on the proliferation of human non-small cell lung cancer (NSCLC) and explore the possible molecular mechanism.
METHODS:Cultured human NSCLC A549 cells were treated with 0.4, 0.8, 1.2, 1.6, and 2.0 g/L matrine for 24, 48 or 72 h. CCK-8 assay was used for measuring the changes in A549 cell viability. The morphological changes of the cells were observed under a fluorescence microscope, and flow cytometry was employed for analyzing the cell apoptosis. The effects of matrine and the PI3K specific inhibitor LY294002 (10 nmol/L) on AKT pathway and autophagy-related proteins in A549 cells were investigated using Western blotting.
RESULTS:Matrine significantly inhibited the proliferation of A549 cells in a time- and dose-dependent manner ( < 0.05). At the concentration of 1.6 g/L or higher, matrine caused obvious cell shrinkage and fragmentation and significantly increased floating cells; autophagy vacuoles could be observed in the cells after acridine orange staining. Within the concentrations range of 0.8-1.6 g/L, matrine time- and dosedependently increased the cell apoptosis. Treatment of the cells with 1.6 g/L matrine and 10 nmol/L LY294002 resulted in significantly lowered expressions of p-AKT and p-mTOR proteins and increased the expression of light chain 3B (LC 3B), an autophagy-related protein, as compared with those in the control cells ( < 0.05).
CONCLUSIONS:We demonstrate that matrine inhibits the proliferation and induces autophagy and apoptosis of A549 cells by deactivating AKT pathway, suggesting the potential of matrine as an anti-cancer agent for lung cancer.
