Abstract 2131: Tanshinone IIA can decrease growth factor receptors expression and dural-block both Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways to inhibit human breast cancer BT-20 cells

Abstract

Abstract Background : Tanshinone IIA (Tan-IIA, C19H18O3) with anti-inflammatory activities and antioxidant properties, is one of the diterpine quinones extracted from Salviae miltiorrhizae radix (Danshen). Tan-IIA can inhibit many human cancer cell lines through different molecular mechanisms. The phosphoinositide-3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) and RAS/RAF/MEK/ERK pathways are two of the most frequently dysregulated kinase cascades in human cancer. Transmembrane tyrosine kinase has been strongly implicated in the proliferation, survival, and metastasis of human tumors. Both pathways represent important signal transduction mechanisms that facilitate the proliferation and survival of cancers driven by growth factor receptors, such as vascular endothelial growth factor receptor (VEGFR), insulin-like growth factor-I receptor (IGF-IR), or epidermal growth factor receptor (EGFR). Targeting both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR Pathways for suppressing inhibitor resistant cells is necessary because the individual downstream components of these signaling cascades either through epigenetic modification or somatic mutation are also known to be frequently altered in cancer, thus contributing to resistance to anticancer therapies and tumorigenesis. Material and methods: In the present study, the human breast cancer BT-20 cells were treated with Tan-IIA in vitro. The cytotoxicity of Tan-IIA was evaluated by MTT assay. The effects of Tan-IIA on the protein expressions of EGFR, IGF-IR, VEGFR, PI3K, AKT, mTOR, Ras, Raf, MEK and ERK and β-actin in the BT-20 cells were examined by western blot analysis. Results: The results showed that Tan-IIA can induce the proliferation inhibition with time and dose dependent and inhibit the activity of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways. In addition, it was showed that Tan-IIA treatment inhibited the protein expression levels of EGFR, VEGFR and IGF-IR significantly. Conclusions: These findings indicated that one of the molecular mechanisms for Tan-IIA to inhibit BT-20 cells maybe through inhibiting the protein expression levels of EGFR, VEGFR, IGF-IR and both Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways. The use of Tan-IIA for breast cancer may become a feasible novel therapy option. Further studies are warranted to elucidate its mechanisms fully. Citation Format: Chin Cheng Su. Tanshinone IIA can decrease growth factor receptors expression and dural-block both Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways to inhibit human breast cancer BT-20 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2131. doi:10.1158/1538-7445.AM2017-2131