ABSTRACT
Objective: To explore the anti-lung cancer mechanism of Maimendong Tang and Qianjin Weijingtang (Jin Fang) by detecting the expression profiles of long noncoding RNA (lncRNA) and mRNA in mice tumor tissues of orthotopic Lewis lung cancer model. Method: C57BL/6 mice were randomly divided into normal group, model group and Jin Fang group (20 g·kg-1·d-1). After successful establishment of Lewis lung cancer model in situ in mice, Jin Fang was given orally the next day after treatment. Using gene chip technology, differential lncRNA and mRNA closely related with Jin Fang' s anti-lung cancer effect were detected, and cluster analysis was performed. The key lncRNA and mRNA were screened out by t-test and fold change of differential expression. Bioinformatic methods were used to predict target genes regulated by differential lncRNA, and functional and pathway analysis was performed. The histopathological technique was used to detect the differences in the tumor tissue of each group under light microscope. Result: lncRNA and mRNA chip hybridization results showed that Jin Fang regulated differential expressions of 887 lncRNA, in which 442 were up-regulated and 445 were down-regulated (PPConclusion: Jin Fang may exert its anti-lung cancer effect by regulating the expressions of multiple lncRNAs and mRNAs, and down-regulating related signaling pathways.
ABSTRACT
5-Hydroxymethylfurfural (5-HMF), a water-soluble compound extracted from wine-processed Fructus corni, is a novel hepatic protectant for treating acute liver injury. The present study was designed to investigate the protective effect of 5-HMF in human L02 hepatocytes injured by D-galactosamine (GalN) and tumor necrosis factor-α (TNF-α) in vitro and to explore the underlying mechanisms of action. Our results showed that 5-HMF caused significant increase in the viability of L02 cells injured by GalN/TNF-α, in accordance with a dose-dependent decrease in apoptotic cell death confirmed by morphological and flow cytometric analyses. Based on immunofluorescence and Western blot assays, we found that GalN/TNF-α induced ER stress in the cells, as indicated by the disturbance of intracellular Ca(2+) concentration, the activation of protein kinase RNA (PKR)-like ER kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), and expression of ATF4 and CHOP proteins, which was reversed by 5-HMF pre-treatment in a dose-dependent manner. The anti-apoptotic effect of 5-HMF was further evidenced by balancing the expression of Bcl-2 family members. In addition, the knockdown of PERK suppressed the expression of phospho-PERK, phospho-eIF2α, ATF4, and CHOP, resulting in a significant decrease in cell apoptosis after the treatment with GalN/TNF-α. 5-HMF could enhance the effects of PERK knockdown, protecting the cells against the GalN/TNF-α insult. In conclusion, these findings demonstrate that 5-HMF can effectively protect GalN/TNF-α-injured L02 hepatocytes against ER stress-induced apoptosis through the regulation of the PERK-eIF2α signaling pathway, suggesting that it is a possible candidate for liver disease therapy.
Subject(s)
Humans , Apoptosis , Cornus , Chemistry , Endoplasmic Reticulum Stress , Eukaryotic Initiation Factor-2 , Genetics , Metabolism , Furaldehyde , Pharmacology , Galactosamine , Metabolism , Hepatocytes , Cell Biology , Metabolism , Liver , Cell Biology , Metabolism , Plant Extracts , Pharmacology , Protective Agents , Pharmacology , Signal Transduction , Tumor Necrosis Factor-alpha , Genetics , Metabolism , eIF-2 Kinase , Genetics , MetabolismABSTRACT
Objective To investigate the protein and mRNA levels of Rac1 in glioma tissues,and explore the correlation of Rac1 with pathological grades. Methods Immunofluorescence,RT-PCR and Western blotting were used to detect the protein and mRNA levels of Rac1 in 45 cases of gliomas tissues and 10 cases of normal brain tissues. Results The results indicated that normal brain tissues showed no protein and mRNA expressions of Rac1, and that of Rac1 highly expressed in glioma tissues (42/45 at most). The spearman correlation analysis revealed that the levels of transcription and expression of Rac1 were positively correlated to the tumor grades; positive expression rate of Rac1 in high grade of glioma was statistically higher than that in low grade of glioma. Conclusion The high expressions of Rac1 in the glioma are closely correlated to the tumor cell invasion and metastasis, which can be used as a marker indicating the malignance and proliferation of glioma.