Effects of tanshinones mediated by forkhead box O3a transcription factor on the proliferation and apoptosis of lung cancer cells

According to global cancer statistics in 2012, lung cancer (LC) was the most frequently diagnosed cancer and the leading cause of cancer-associated mortality among males worldwide. Owing to the limited therapeutic approaches available, novel methods for treating LC are required. Tanshinones (Ts) have previously been proved to be effective in treating cardiovascular disease, inflammatory disease and cancer, and have been reported to regulate cell proliferation and apoptosis of LC. The underlying molecular mechanism of action of Ts remains unclear. Furthermore, forkhead box O3a (FoxO3a) has been reported to be a critical gene in cell apoptosis. Therefore, the A549 lung cancer cell line was transfected with FoxO3a small interfering RNA (siRNA) or scrambled siRNA, and the cells which exhibited the most successful transfection efficacy were selected for further investigation into the underlying molecular mechanism of the influence of Ts on FoxO3a in LC cells. Various concentrations of Ts were assigned to experimental groups I-IV (5, 10, 20 and 30 µmol/l Ts, respectively). An MTT assay revealed that Ts inhibited cell proliferation in a dose- and time-dependent manner compared with the control group (CON; without Ts administration) with a maximal dose of 20 µmol/l at 72 h treatment (P<0.05). Similarly, compared with CON, flow cytometry results revealed that Ts induce LC cell apoptosis in a dose-dependent manner (P<0.05). Consistently, the expression levels of FoxO3a mRNA and protein were restored following treatment with Ts in a dose-dependent manner, alongside caspase-3 activation. On the basis of these results, we hypothesize that Ts regulate LC cell proliferation and apoptosis by triggering an apoptotic cascade through the FoxO3a/caspase-3 signaling pathway.