Propofol induces apoptosis of non-small cell lung cancer cells via ERK1/2-dependent upregulation of PUMA
S.-G. Xing, K.-J. Zhang, J.-H. Qu, Y.-D. Ren, Q. Luan Department of Respiratory, the Central Hospital of Linyi, Yishui, Linyi, Shandong, China. mcgilld@126.com
OBJECTIVE: Propofol is one of the most commonly used intravenous anesthetic agents used in cancer resections, but the effect of propofol on non-small cell lung cancer (NSCLC) remains unclear. Previous researches have reported that propofol can inhibit extracellular signal-regulated kinase (ERK) 1/2 phosphorylation or activate p53-upregulated modulator of apoptosis (PUMA) signaling, resulting in apoptosis. In addition, PUMA is negatively regulated by ERK1/2 activation. In the present work, we determined the effect of propofol on NSCLC A549 cells and explored its signaling pathway.
MATERIALS AND METHODS: A549 cells were treated with different concentrations of propofol (1-10 μg/mL) for 6 h. After washing, cells were cultured in Dulbecco’s Modified Eagle Medium supplemented with 10% fetal bovine serum and antibiotics for another 72 h. Cell survival and apoptosis were determined by MTT, flow cytometry, and TUNEL analyses. To assess whether propofol functions via ERK1/2 and PUMA signaling pathways, A549 cells were transfected with small interfering RNA (siRNA) to target PUMA, or treated with human recombinant ERK1/2 (hrERK1/2) to activate ERK1/2.
RESULTS: Propofol treatment inhibited viability and induced apoptosis of A549 cells in a dose-dependent manner in vitro. Propofol inhibited phosphorylation of ERK1/2 (pERK1/2) and increased ERK1/2-dependent PUMA expression. Knockdown of PUMA by siRNA or treatment with hrERK1/2 to activate ERK1/2 blocked propofol-induced apoptosis and cell viability. Upregulation of PUMA expression by propofol requires pERK1/2 inactivation.
CONCLUSIONS: Propofol inhibits viability and induces apoptosis of A549 cells via an ERK1/2-dependent PUMA signaling.
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To cite this article
S.-G. Xing, K.-J. Zhang, J.-H. Qu, Y.-D. Ren, Q. Luan
Propofol induces apoptosis of non-small cell lung cancer cells via ERK1/2-dependent upregulation of PUMA
Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 13
Pages: 4341-4349
DOI: 10.26355/eurrev_201807_15431