Background
Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, effectively inhibiting cholesterol synthesis. Previous research findings showed that lovastatin markedly suppressed tumor cell proliferation and metastasis and induced apoptosis. The present study aimed to determine the underlying mechanism of the suppressive effect of lovastatin on the growth of human lung cancer cells.
Conclusions
Collectively, the findings presented in this study confirmed that lovastatin can inhibit A549 cell proliferation by regulating the ERK1/2 and COX-2 pathways.
Methods
The A549 cell line was treated with different concentrations of lovastatin. Subsequently, cell proliferation and colony formation were analyzed, along with the expression of apoptosis-related proteins (ERK1/2, c-JUN, COX-2, BCL-2, and BAX) by western blotting and immunofluorescence staining. Experimental data were analyzed with SPSS 25.0 and expressed as the mean ± SEM. One-way ANOVA or two-way independent samples t-test were used.
Results
The results confirmed that lovastatin suppressed cell viability and reduced the numbers of cell colonies, and a concentration-dependent response was observed with increasing lovastatin concentrations (P<0.05). Accordingly, these suppressive effects were related to decreased protein expression levels of p-ERK1/2/ERK1/2, p-c-JUN/c-JUN, COX-2, and BCL-2 and increased BAX protein expression (P<0.05). Furthermore, we conducted an experimental intervention with low-dose LPS+ATP to stimulate A549 cell growth, and then examined the proliferation and apoptosis of A549 cells after LPS+ATP+50 µM lovastatin intervention. The principal finding of this research was that lovastatin still suppressed A549 cell growth after LPS+ATP stimulation via modulation of ERK1/2, c-JUN, COX-2, BCL-2, and BAX protein levels (P<0.05). Conclusions: Collectively, the findings presented in this study confirmed that lovastatin can inhibit A549 cell proliferation by regulating the ERK1/2 and COX-2 pathways.