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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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In this study, we firstly studied whether H3K27me3 modification is a mechanism of miR-129-5p downregulation in breast cancer and further investigated the functional role of miR-129-5p in epithelial-tomesenchymal transition (EMT) and in multi-drug resistance (MDR) of the cancer cells. MATERIALS AND METHODS: Immunoprecipitation (IP) and Chromatin Immunoprecipitation (ChIP) assay were performed to detect the association among SOX4, EZH2 and H3K27me3 and their enrichment in the promoter region of miR- 129-2. Western blot and immunofluorescent staining were performed to detect the expression of epithelial and mesenchymal markers. MTT assay was applied to test drug sensitivity. RESULTS: Enforced EZH2 and SOX4 expression resulted in suppressed miR-129-5p level in MCF-7 cells. There was an interaction among SOX4, EZH2 and H3K27me3 modification and they were significantly enriched in the region upstream of transcription start of miR-129-2. MCF-7 cells transfected with miR-129-5p mimics had significantly suppressed SOX4 expression. MCF-7 cells with miR-129-5p overexpression had significantly restored E-cadherin expression and suppressed N-cadherin and Vimentin expression. The drug sensitivity assay showed that miR-129-5p substantially reduced IC50 of ADM, VCR and PTX in MCF-7/ADM cells CONCLUSIONS: There is a reciprocal regulation between miR-129-5p and SOX4 via the SOX4/EZH2 complex mediated H3K27me3 modification in breast cancer cells. MiR-129-5p is an important miRNA modulating EMT and MDR in breast cancer cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ovarian cancer accounted for the first cause of death in female reproductive system tumor even with the operation and chemotherapy. We sought to evaluate the therapeutic potential of p53 up-regulated modulator of apoptosis (PUMA) in ovarian cancer. MATERIALS AND METHODS: An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents, was used to treat two different ovarian cancer cell lines. The mechanism of PUMA-mediated growth suppression and apoptosis was investigated by analysis of caspase-9 activation and the change of mitochondrial membrane potential (Δψm). RESULTS: The exogenous PUMA was expressed 6 h after Ad-PUMA infection, which increased the chemosensitivity of the cancer cells and decreased the IC50 of chemotherapeutic agents compared with uninfected cells. The apoptotic percentage of OVCAR-3 and SKOV3 increased greatly compared with Taxol or Cisplatin alone. There was shear zone in caspase-9 and Δψm decrease after Ad-PUMA infection which suggested apoptosis started in mitochondrial mediated pathway. CONCLUSIONS: PUMA plays a role in suppressing tumor growth and sensitizing ovarian cancer cells to anticancer drugs and may be a promising tool for cancer biotherapy. [ABSTRACT FROM AUTHOR]