RESUMO
Currently, developing therapeutic strategies for chondrosarcoma (CS) remains important. Sennoside A (SA), a dianthrone glycoside from Senna and Rhubarb, is widely used as an irritant laxative, weight-loss agent, or dietary supplement, which possesses various bioactive properties such as laxative, antiobesity, and hypoglycemic activities. For the first time, our results suggested that cell proliferation and metastasis were inhibited by SA in CS SW1353 cells. SA induced cell growth arrest by inhibiting cell proliferation. The changes of N-cadherin and E-cadherin levels, the markers associated with epithelial mesenchymal transition (EMT), suggested the EMT-related mechanism of SA in inhibiting cell metastasis. Besides, SA significantly stimulated apoptosis in CS SW1353 cells, leading to cell death. The increase of Bax/Bcl2 ratio confirmed that the internal mitochondrial pathway of apoptosis was regulated by SA. In addition, the prediction of network pharmacology analysis suggested that the possible pathways of SA treatment for CS included the Wnt signaling pathway. Notably, the protein levels of the components in the Wnt pathway, such as Wnt3a, ß-catenin, and c-Myc, were downregulated by SA in CS SW1353 cells. To sum up, these results demonstrated that the suppression of the growth, metastasis and the stimulation of cytotoxicity, and apoptosis mediated by SA in CS SW1353 cells were possibly caused by the inhibition of the Wnt/ß-catenin pathway, indicating an underlying therapeutic prospect of SA for chondrosarcoma.
RESUMO
Metformin (MET), the most common medicine for type 2 diabetes (T2DM), improves insulin sensitivity by targeting the liver, intestine and other organs. Its impact on expression of the solute carrier (Slc) transporter genes have not been reported in the mechanism of insulin sensitization. In this study, we examined Slc gene expression in the liver and colon of diet-induced obese (DIO) mice treated with MET by transcriptomic analysis. There were 939 differentially expressed genes (DEGs) in the liver of DIO mice vs lean mice, which included 34 Slc genes. MET altered 489 DEGs in the liver of DIO mice, in which 23 were Slc genes. Expression of 20 MET-responsive Slc DEGs was confirmed by qRT-PCR, in which 15 Slc genes were altered in DIO mice and their expressions were restored by MET, including Slc2a10, Slc2a13, Slc5a9, Slc6a14, Slc7a9, Slc9a2, Slc9a3, Slc13a2, Slc15a2, Slc26a3, Slc34a2, Slc37a1, Slc44a4, Slc51b and Slc52a3. While, there were only 97 DEGs in the colon of DIO mice with 5 Slc genes, whose expression was not restored by MET. The data suggest that more genes were altered in the liver over the colon by the high fat diet (HFD). There were 20 Slc genes with alteration confirmed in the liver of DIO mice and 15 of them were restored by MET, which was associated with improvement of insulin sensitivity and obesity. The restoration may improve the uptake of glucose, amino acids, mannose, fructose, 1,5-anhydro-D-glucitol and bumetanide in hepatocytes of the liver of DIO mice. The study provides new insight into the mechanism of metformin action in insulin sensitization and obesity.
