ABSTRACT
Aim To explore the mechanism of Hispolon in the treatment of colon cancer by network pharmacology and cell experimental validation. Methods The potential targets of Hispolon were obtained from the Swiss Target Prediction website, and intersected with colon cancer targets from GeneCards and OMIM databases. The protein-protein interaction network of targets was built by the STRING11. 0 database. Meanwhile , the core targets of PPI network was explored by Cytoscape 3. 7. 2 software. Furthermore, the GO and KEGG pathway enrichment were analyzed by Metas- cape database. Finally, Western blotting was used to verify the regulation of Hispolon on some key targets in colon cancer cell SW480. Results Sixty-nine com-mon targets of Hispolon and colon cancer were obtained, which were colon cancer therapeutic targets. The core targets included BCL-2L1, EP300, CDK1, AR, MTOR and EGFR. The enrichment analysis showed that Hispolon played a role in the treatment of colon cancer by regulating the pathways in cancer, PI3K-Akt signaling pathway, prostate cancer and Mi- croRNAs in cancer. And the key targets in the pathway involved core targets such as BCL-2 LI, EP300, CDK1, MTOR and EGFR. Cell experiments confirmed that Hispolon promoted SW480 cell apoptosis by down- regulating the expression of target proteins BCL-2L1 and mTOR. Conclusions The discussion of the molecular mechanism of Hispolon in the treatment of colon cancer suggests that Hispolon may play a role in the treatment of colon cancer through multiple targets and multiple pathways. The results provide a scientific basis for the elucidation of the mechanisms and clinical application of Hispolon against colon cancer.
ABSTRACT
BACKGROUND: Hispolon has been shown to possess antitumor effects in various cancer cells. However, the underlying mechanisms are not fully understood. In this study, we evaluated the sensitizing effect of hispolon on TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human renal carcinoma cells. METHODS: Apoptosis was analyzed by using cell-based cytometer. The mRNA levels were assessed by reverse transcription-PCR. Bax activation was determined by oligomerization and fluorescence-activated cell sorting with Bax-NT monoclonal antibody. The protein expression was measured by Western blotting. RESULTS: Hispolon induced up-regulation of Bim and death receptors expression at the post-translational level. CONCLUSIONS: Hispolon enhanced TRAIL-mediated apoptosis in renal carcinoma cells, but not in normal cells.