RESUMO
PURPOSE: To investigate the effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue squamous cell carcinoma cell line CAL27. METHODS: The effect of BMS-777607 on proliferation of CAL27 was detected by MTT method, clone formation assay and EdU cell imaging. Morphological changes of apoptosis of CAL27 cells induced by BMS-777607 were observed by Heochst33342 staining. JC-1 staining was used to detect the changes of mitochondrial membrane potential of CAL27 cells treated with BMS-777607. Western blot was used to detect the effect of BMS-777607 on the expression of proliferation protein Akt, p-Akt and apoptosis-related proteins Bcl-2, Cleaved caspase-3, Bax and Parp in CAL27 cells. The data were analyzed using SPSS 22.0 software package. RESULTS: BMS-777607 inhibited proliferation and promoted apoptosis of CAL27 cells in a concentration-dependent mannerï¼Pï¼0.05ï¼. It also inhibited the expression of Bcl-2 and p-Akt and promoted the expression of Bax, Cleaved caspase-3 and Parp protein (Pï¼0.05). CONCLUSIONS: BMS-777607 can inhibit proliferation and promote apoptosis of CAL27 cells.
Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Aminopiridinas , Apoptose , Proteínas Reguladoras de Apoptose , Carcinoma de Células Escamosas/metabolismo , Caspase 3/farmacologia , Caspase 3/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/uso terapêutico , Piridonas , Língua , Neoplasias da Língua/tratamento farmacológico , Proteína X Associada a bcl-2/farmacologiaRESUMO
OBJECTIVE: This study aims to study the effect of the enhancer of zeste homolog 2 (EZH2) inhibitor GSK126 on the proliferation and apoptosis of human tongue squamous cell carcinoma cells in vitro and explore its related mechanisms in order to obtain insights into the clinical treatment of tongue squamous cell carcinoma. METHODS: Different concentrations of GSK126 were applied to CAL-27 cells of tongue squamous cell carcinoma, and the effects of drugs on cell proliferation were detected through methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining. Hoechst33342 fluorescence staining and the JC-1 method were used in observing apoptosis. The expression levels of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK), Bax, Bcl-2, and Cleaved caspase-9 in Cal-27 cells were detected through Western blot. RESULTS: GSK126 inhibited CAL-27 cell proliferation and promoted apoptosis. GSK126 down-regulated the expression of p-ERK and Bcl-2 and increased the expression of Bax and Cleaved caspase-9 (P<0.05). CONCLUSIONS: GSK126 can inhibit the proliferation of CAL-27 cells in tongue squamous cell carcinoma and promote its apoptosis, and the related mechanism may be associated with the inhibition of the MEK/ERK signaling pathway and activation of the Bax/Bcl-2 pathway.
Assuntos
Apoptose , Carcinoma de Células Escamosas , Neoplasias da Língua , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste , Humanos , Indóis , Piridonas , Neoplasias da Língua/tratamento farmacológicoRESUMO
BACKGROUND: Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson's disease (PD). However, the results have been inconsistent so far. OBJECTIVES: The aim of the present study was to clarify the potential relationship of uric acid with PD. METHODS: Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. RESULTS: Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = -0.65, 95% CI [-0.84, -0.46], Z = 6.75, p <0.001; Non-Asia: SMD = -0.25, 95% CI [-0.43, -0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = -0.53, 95% CI [-0.70, -0.35], z = 5.98, p <0.001; men: SMD = -0.66, 95% CI [-0.87, -0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). CONCLUSIONS: Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate the risk and progression of PD.