Tanshinone IIA exerts antitumor activity against vestibular schwannoma cells by inhibiting the expression of hypoxia-inducible factor-1 alpha

Abstract

The aim of the present study was to evaluate the effect of the herbal medicine, tanshinone IIA (Tan IIA), on vestibular schwannoma (VS) cells and assess the functional targets of Tan IIA. HEI-193 cells and Nf2-/-mouse Schwann (SC4) cells were used to investigate the inhibitory effects of Tan IIA on VS. Cell viability was measured using an MTT assay and apoptosis was assessed by flow cytometry. Western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed to assess the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and its signaling pathways. In addition, the effect of Tan IIA on HIF-1a transcription was determined using a luciferase reporter assay. Schwannoma cell proliferation was observed to be inhibited as the Tan IIA concentration increased under normoxic and hypoxic conditions. Furthermore, Tan IIA induced apoptosis in the HEI-193 cells and inhibited the protein expression of HIF-1 alpha in the HEI-193 cells under hypoxia, thus repressing the transcriptional activity of HIF-1 alpha. The present study demonstrated that HIF-1 alpha is expressed in hypoxic VS cells and Tan IIA inhibits VS cells by suppressing the activity of HIF-1 alpha. In conclusion, these results indicate that Tan IIA is a potential chemotherapeutic agent for the treatment of VS.