The aim of the present study was to investigate cobra
neurotoxin (
cobrotoxin) activity in A549 cell lines transplanted into nude mice, and to explore its molecular mechanism. The
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the growth inhibition rate of
cobrotoxin in human lung A549
adenocarcinoma cells and HFL1 lung fibroblasts. Cell colony formation assays were performed to determine the effect of
cobrotoxin on A549 cell colony formation, and transmission electron microscopy was used to detect
cobrotoxin autophagy. In addition, western blot analysis was performed to determine the effect of 3-methyl
adenine (3-MA) activity on the inhibition of autophagy,
SB203580 inhibition of the p38-mitogen-activated
protein kinase (MAPK) pathway, and
Beclin 1, LC3, p62, p38 and phosphorylated (p)-p38
protein expression. Nude mice were injected with human lung A549 cells, and intervention and control groups were compared with regard to
tumor suppression. The MTT assay revealed that various concentrations of
cobrotoxin inhibited growth of A549 cells, but not HFL1 cells. A549 cell colony formation decreased and autophagosome activity was significantly increased compared with the controls. Following 3-MA administration,
SB203580 autophagosome activity decreased, and following
cobrotoxin administration,
Beclin 1, p-p38, and LC3-II
protein expression significantly increased, whereas p62 expression significantly decreased. Following 3-MA inhibition of autophagy,
Beclin 1, LC3-II and p62 expression increased. Furthermore, following
SB203580 inhibition of the p38-MAPK pathway,
Beclin 1, p-p38, LC3-II and p62
protein expression increased.
Cobrotoxin exhibited inhibitory activity on the human
lung cancer A549 cells transplanted into the nude mice, suppressing the
tumor growth rate by 43.4% (
cobrotoxin 40 μg/kg group). However, following the addition of 3-MA (10 mmol/kg) and
SB203580 (5 mg/kg), the suppression of the
tumor growth rate decreased significantly.
Cobrotoxin inhibits the growth of human
lung cancer A549 cells in vitro and A549 cells transplanted into nude mice. Furthermore, the induction of autophagy may be associated with the activation of the p38-MAPK pathway.