Tanshinone IIA inhibits gastric carcinoma AGS cells by decreasing the protein expression of VEGFR and blocking Ras/Raf/MEK/ERK pathway

The RAS/RAF/MEK/ERK pathway is one of the most frequently dysregulated kinase cascades in human cancer, that facilitate the proliferation and survival of cancers driven by growth factor receptors. Tanshinone IIA (Tan-IIA) was extracted from Danshen (Salviae Miltiorrhizae Radix). Tan-IIA inhibition of the proliferation of gastric cancer are well documented, but the molecular mechanisms of Tan-IIA inhibition of gastric cancer have not been well elucidated. We evaluated the protein expression of vascular epidermal growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2), Ras, Raf, MEK, ERK, PARP, caspase-3 and -actin in AGS cells by western blotting. The results showed that AGS cells treated with Tan-IIA upregulated the protein expression of PARP and caspase-3 but decreased VEGFR, HER2, Ras, Raf, MEK and ERK time- and dose-dependently. These findings demonstrated that Tan-IIA inhibited human gastric cancer AGS cells; one of the molecular mechanisms may be through decreasing the protein expression of VEGFR and HER2, then blocking the Ras/Raf/MEK/ERK pathway to induce the activation of PARP and caspase-3 to induce apoptosis.