Abstract 2185: Sann-Joong-Kuey-Jian-Tang can inhibit human breast cancer cells through dural- blocking both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways

Abstract

Abstract Sann-Joong-Kuey-Jian-Tang (SJKJT) consists of 17 species of medicinal herbs, is a traditional Chinese medicine prescription, and has been used as complementary medication for a number of types of solid cancer in Taiwan. Transmembrane tyrosine kinase has been strongly implicated in the growth, survival, and metastasis of a wide variety of human tumors. 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 were well documented. 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), human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR).The individual downstream components of these signaling cascades either through somatic mutation or epigenetic modification, are also known to be frequently altered in cancer, thus contributing to tumorigenesis and resistance to anticancer therapies. Targeting both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR Pathways for suppressing Inhibitor Resistant Cells is necessary. In the present study, the human breast cancer BT-20 and MCF-7 cells were treated with SJKJT in vitro. The cytotoxicity of SJKJT were evaluated by 3–(4,5–dimethylthiazol–2–y1)–2,5–diphenyltetrazolium bromide (MTT) assay. The effects of SJKJT on the protein expressions of VEGFR, IGF-IR, PI3K, AKT, mTOR, Ras, Raf, MEK and ERK and β-actin in the BT-20 and MCF-7 cells were examined by western blot analysis. The results showed that SJKJT can induce the proliferation inhibition with time and dose dependent. As a potential mechanism, it was noted that SJKJT treatment significantly inhibited the activity of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways, which played a protective role against the cytotoxicity. In addition, it was demonstrated that SJKJT treatment inhibited the protein expressions of VEGFR, EGFR and IGF-IR significantly. These results suggest that one of the molecular mechanisms for SJKJT to inhibit breast cancer BT-20 and MCF-7 cells maybe through inhibiting the protein expressions of VEGFR, EGFR, IGF-IR and both Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways. The use of traditional chinese medicine prescription SJKJT may become a feasible novel therapy option. Further studies are warranted to fully elucidate its mechanisms of action. Citation Format: CHIN CHENG SU. Sann-Joong-Kuey-Jian-Tang can inhibit human breast cancer cells through dural- blocking both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2185.