title: Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-κB signal.
abstract: Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.
authors.affiliation: Department of Gynecology, the People's Hospital of Laiwu, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Oncology, the People's Hospital of Rizhao, Rizhao, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Gynecology and Obstetrics, the First People's Hospital of Jinan, Jinan, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, the People's Hospital of Weifang, Weifang, China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D015742:Propofol / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D020011:Protective Agents; D020780:Matrix Metalloproteinase 9; D015742:Propofol