Tanshinone IIA can inhibit MiaPaCa‑2 human pancreatic cancer cells by dual blockade of the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways

Su,Chin‑Cheng

doi:10.3892/or.2018.6670

Tanshinone IIA can inhibit MiaPaCa‑2 human pancreatic cancer cells by dual blockade of the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways

Authors:
- Chin‑Cheng Su
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Affiliations: Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.
Published online on: August 23, 2018 https://doi.org/10.3892/or.2018.6670
Pages: 3102-3111

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Abstract

Tanshinone IIA (Tan‑IIA; C19H18O3) is derived from Danshen (the roots of Salvia miltiorrhiza), and has been reported to possess anti‑inflammatory and antioxidant activities. Tan‑IIA can inhibit BxPC‑3 human pancreatic cancer cells in vitro through inducing endoplasmic reticulum stress and apoptosis via mitochondrial pathways. However, the efficacy and molecular mechanisms of Tan‑IIA in human pancreatic cancer have not yet been elucidated. The transmembrane tyrosine kinases, including insulin‑like growth factor 1 receptor (IGF1R), vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor (EGFR) have been implicated in the survival and metastasis of cancer. In addition, the Ras/Raf/mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑regulated kinase (ERK) and phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways are the most commonly dysregulated kinase cascades in human cancer. The present study aimed to investigate the efficacy and molecular mechanisms of Tan‑IIA in MiaPaCa‑2 human pancreatic carcinoma cells. The protein expression levels of EGFR, IGF1R, VEGFR, Ras, PI3K, AKT, mTOR, Raf, MEK, ERK and phosphatase and tensin homolog (PTEN) were detected in Tan‑IIA‑treated MiaPaCa‑2 cells by western blotting. The results demonstrated that the protein expression levels of EGFR, IGF1R, VEGFR, Ras, Raf, MEK, ERK, PI3K, AKT, mTOR and PTEN were decreased in MiaPaCa‑2 cells treated with various concentrations of Tan‑IIA for different durations. In conclusion, these findings indicated that Tan‑IIA may inhibit MiaPaCa‑2 human pancreatic cancer cells; the molecular mechanisms underlying this inhibitory effect may be involved in downregulating EGFR, IGF1R and VEGFR expression, and dual blockade of the Ras/Raf/MERK/ERK and PI3K/AKT/mTOR pathways.

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