ABSTRACT
BACKGROUND: Antiapoptosis is a major factor in the resistance of tumor cells to chemotherapy and radiotherapy. Thus, activation of cell pyroptosis may be an effective option to deal with antiapoptotic cancers such as esophageal adenocarcinoma (EAC). METHODS: Differential expression of ubiquitin-like versus PHD and ring finger structural domain 1 (UHRF1) in EAC and near normal tissues was analyzed, as well as the prognostic impact on survival in EAC. Also, the same study was done for globular adiponectin (gAD). Simultaneously, the mRNA expression of UHRF1 was observed in different EAC cell lines. Real time cellular analysis (RTCA) was used to detect cell proliferation, and flow cytometry and inverted fluorescence microscopy were used to detect pyroptosis. Biocredit analysis was conducted to observe the correlation between UHRF1 and key pyroptosis proteins. OD values and CCK8 assay were used to determine the effect of miR-378a-3p on EAC cells. Quantitative real-time polymerase chain reaction and Western blot were used to detect the correlation between UHRF1, gAD, and miR-378a-3p in EAC cells. Moreover, in vivo and in vitro experiments were performed to detect the relevant effects on tumor migration and invasion after inhibiting UHRF1 expression. RESULTS: UHRF1 was negatively correlated with the survival of patients with EAC, while miR-378a-3p showed the opposite effect. Additionally, gAD promoted EAC cell pyroptosis, upregulated miR-378a-3p, and significantly inhibited the proliferation of EAC cells. gAD directly reduced UHRF1 expression in EAC cells by upregulating miR-378a-3p. In cell migration and invasion assays, inhibition of UHRF1 expression significantly suppressed EAC cell metastasis. In animal experiments, we again demonstrated that gAD induced pyroptosis in EAC cells by inhibiting the expression of UHRF1. CONCLUSION: gAD-induced upregulation of miR-378a-3p significantly inhibited the proliferation of EAC by targeting UHRF1. Therefore, gAD may serve as an alternative therapy for chemotherapy- and radiation-refractory EAC or other cancers with the same mechanism of pyroptosis action.
ABSTRACT
Background:Functional dyspepsia (FD)with anxiety and gastric hypersensitivity is still one of the therapeutic difficulties in clinic. Gastrodin (Gas)may have dual effects of modulating gastric sensitivity and anxiety. Aims:To investigate the effect of Gas on gastric sensitivity and anxiety-like behavior in FD with anxiety-like gastric hypersensitivity in rats. Methods:Forty rats were randomly divided into control group,model group,buspirone group,low-dose Gas group and high-dose Gas group. Maternal separation,acute gastric irritation and restraint stress were sequentially performed to induce FD model with anxiety-like gastric hypersensitivity. At the 8th week,rats in control group and model group were intraperitoneally injected with 0. 9% NaCl solution 2. 0 mL/ kg,rats in buspirone group were given buspirone 3. 125 mg/kg,and rats in low- and high-dose Gas groups were given 62. 5,125. 0 mg/ kg Gas,respectively. The course was 7 days. Then elevated plus maze (EPM),open field test,abdominal withdrawal reflex (AWR)and electromyography (EMG) were performed. Results:Compared with control group,EPM test showed that proportions of open arms entries and duration were significantly decreased (P < 0. 01);open field test showed that virtual central grids duration (P < 0. 05),number of virtual grids climbed and times of lifting were significantly decreased (P < 0. 01);when gastric balloon dilatation pressure was equal or greater than 40 mm Hg,AWR score,area under ROC curve (AUC)of EMG was significantly increased in model group (P < 0. 05). Compared with model group,above-mentioned indices in low- and high-dose Gas groups were significantly ameliorated (P < 0. 05). Conclusions:Gas could influence the gastric sensitivity and anxiety-like behavior of the brain-stomach axis regulated anxiety-like gastric hypersensitivity in FD rat model.
ABSTRACT
Objective To investigate the effect and mechanism of DADS in inhibiting the proliferation and inducing apoptosis of gastro-esophageal cancer cells in vitro.Methods The gastro-esophageal adenocarcinoma cells OE1 9 were treated by DADS of different concentrations in vitro.Morphologic changes were observed by the microscope and MTT assay was performed to test the growth-inhibitory effect of DADS on OE1 9 cells.Apoptosis rate of OE1 9 treated with different concentrations of DADS was measured by flow cytometry.Real-time PCR was used to detect DADS-induced effects on mRNA expressions of Caspase-3 ,Caspase-9 ,Bcl-2 ,Bax and NF-κB in OE1 9 cells.Results DADS inhibited the proliferation of OE19 cells in a dose-dependent manner.The apoptosis rate of OE19 cells was 14.0%,25.4% and 19.0% and 27.2%,respectively,when treated with 40 and 80μg/mL DADS for 24 h and 48 h.Real-time PCR assay showed that DADS could enhance mRNA expression levels of Caspase-3 and Caspase-9 and significantly decrease the mRNA expression levels of NF-κB and Bcl-2 and the ratio of Bcl-2/Bax. Conclusion DADS can significantly inhibit the proliferation and induce the apoptosis of gastro-esophageal adenocarcinoma cells via mitochondria-dependent pathways,which may be related to NF-κB and Bcl-2 families.
