Abstract
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. TanshinoneIIA (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 receptor2 (HER2), Ras, Raf, MEK, ERK, PARP, caspase-3 and β-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.
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