Open AccessMetformin promotes apoptosis of A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio and ROS levels
Author(s) -
Ziying Yu,
Fengtao Liu,
Xiaoli Zhang
Publication year - 2021
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v20i9.7
Subject(s) - ampk , metformin , apoptosis , a549 cell , chemistry , reactive oxygen species , pi3k/akt/mtor pathway , flow cytometry , protein kinase a , mtt assay , microbiology and biotechnology , cancer research , kinase , biology , endocrinology , biochemistry , insulin
Purpose: To investigate the influence of metformin on apoptosis of pulmonary carcinoma cells (A549), and the associated mode of action.Methods: Pulmonary carcinoma cells in logarithmic growth phase were treated with graded concentrations of metformin, and the anti-proliferative and apoptotic effects of the drug were measured using MTT assay and flow cytometry, respectively. The levels of reactive oxygen species (ROS) in A549 cell suspension were determined with 2, 7- dihydrodichlorofluorescein diacetate (DCFH-DA) assay. The expression levels of phosphorylated AMP-activated protein kinase (p-AMPK), mammalian target of rapamycin (mTOR), and bax/bcl-2 ratio were measured using Western blotting and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR).Results: Metformin significantly promoted A549 cell apoptosis, but suppressed its proliferative potential in a dose- and time-based fashion. The levels of ROS, superoxide anion and MDA in A549 cells were significantly and dose-dependently increased by metformin (p < 0.05). Moreover, metformin markedly upregulated the mRNA and protein expressions of p-AMPK as well as bax/bcl-2 ratio, but had no impact on the expression level of mTOR (p < 0.05).Conclusion: Metformin promotes apoptosis in A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio, and ROS levels, and hence may play a role in lung cancer therapy.