PMID- 30226540
OWN - NLM
STAT- MEDLINE
DCOM- 20181218
LR  - 20211204
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 40
IP  - 5
DP  - 2018 Nov
TI  - Tanshinone IIA can inhibit MiaPaCa‑2 human pancreatic cancer cells by dual 
      blockade of the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways.
PG  - 3102-3111
LID - 10.3892/or.2018.6670 [doi]
AB  - 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.
FAU - Su, Chin-Cheng
AU  - Su CC
AD  - Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, 
      Changhua 50006, Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
DEP - 20180823
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Abietanes)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 03UUH3J385 (tanshinone)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Abietanes/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Humans
MH  - Pancreatic Neoplasms/*drug therapy/genetics/pathology
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/genetics
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics
MH  - raf Kinases/antagonists & inhibitors/genetics
MH  - ras Proteins/antagonists & inhibitors/genetics
EDAT- 2018/09/19 06:00
MHDA- 2018/12/19 06:00
CRDT- 2018/09/19 06:00
PHST- 2018/01/19 00:00 [received]
PHST- 2018/08/14 00:00 [accepted]
PHST- 2018/09/19 06:00 [pubmed]
PHST- 2018/12/19 06:00 [medline]
PHST- 2018/09/19 06:00 [entrez]
AID - 10.3892/or.2018.6670 [doi]
PST - ppublish
SO  - Oncol Rep. 2018 Nov;40(5):3102-3111. doi: 10.3892/or.2018.6670. Epub 2018 Aug 23.