RESUMO
Objective:To explore the potential molecular mechanism of corylin in the treatment of lung cancer. Method:A549 cells were treated with different concentrations of corylin， and their proliferation was detected using methye thiazolye telrazlium （MTT） reagent. Then the trend analysis and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were conducted to screen the key genes and pathways of corylin against A549 cell proliferation， followed by the verification of sequencing results by real-time polymerase chain reaction （Real-time PCR）. Result:Corylin inhibited the proliferation of A549 cells and regulated the expression of 4 364 genes in cells. The trend analysis revealed that these genes were clustered into 20 distinct modules， among which four were significantly down-regulated， suggesting that corylin exerted the anti-proliferation effect by inhibiting the expression of some genes. The inter-group comparison of differentially expressed genes （DEGs） showed that the elevation in the concentration of corylin resulted in more down-regulated genes but weakened proliferation， consistent with the findings by trend analysis. The GO and KEGG enrichment analysis of 278 DEGs in the high-dose corylin group demonstrated that corylin mainly changed the cellular and metabolic processes， which was attributed to its regulation of steroid biosynthesis， fatty acid metabolism， biosynthesis of unsaturated fatty acids， synthesis and degradation of ketone bodies， and steroid hormone biosynthesis. The Real-time PCR results confirmed that corylin down-regulated the mRNA expression levels of LSS， stearoyl-CoA desaturase （SCD）， 3-hydroxy-3-methylglutaryl-CoA synthase 1 （HMGCS1）， but up-regulated the mRNA expression of recombinant human angiopoietin-like protein 4 （ANGPTL4）， basically consistent with the transcriptomics results. Conclusion:Corylin inhibits A549 cell proliferation and alleviates lung cancer by targeting the related genes in lipid metabolism pathways.
RESUMO
The nuclear-related factor 2 (Nrf2) pathway is the most important mechanism in antioxidant capacity, which regulates the cell's redox homeostasis. In addition, Nrf2 pathway also can inhibit cell apoptosis. The mechanism of boron actions on various organs is well documented. But, it is not known whether boron can also regulate the Nrf2 pathway in the kidneys. Therefore, in this research, the actions of boron on the kidneys of ostrich chicks, especially the antioxidant effects, have been studied. The ostrich chicks were divided into six groups and supplemented with boric acid (BA) (source of boron) in the drinking water (0, 40, 80, 160, 320, 640 mg respectively) to examine apoptotic, antioxidant, biochemical, and histochemical alterations induced by boron administration in the ostrich chick's kidney. The cellular apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. The relative antioxidant enzymes (T-AOC, MDA, GSH-Px, SOD, GR, CAT) and biochemical indices (ALT, AST, ALP, CK, LDH, BUN, CREA, UA) in the kidney were determined by spectrophotometric method. The expression of three important genes in the antioxidant pathway (Nrf2, HO-1, GCLc) was measured by quantitative real-time PCR (qPCR), and the localization of key regulator Nrf2 was examined by immunohistochemistry (IHC) method. Western blotting was also performed to further validate our results. Our results revealed that low doses of boron (up to 160 mg) had positive effect, while high doses (especially 640 mg) caused negative effect on the development of the kidney. The cellular apoptosis was in a biphasic manner by altering the boron quantities. The low doses regulate the oxidative and enzyme activity in the kidney. The IHC and western blot showed maximum localization of Nrf2 in 80 mg/L BA dose group. Furthermore, supplementation of boron at low doses upregulated the expression of genes involved in the antioxidant pathway. Taken together, the study demonstrated that low levels of boron (up to 160 mg) inhibited the cell apoptosis, regulate the enzyme activity, and improved the antioxidant system, thus may encourage the development of the ostrich chick's kidney, while a high amount of boron especially 640 mg/L promoted cell apoptosis and reduced the antioxidant capacity, thus caused negative effect to the ostrich chick's kidney.
