Anti-colorectal cancer effects of scutellarin revealed by genomic and proteomic analysis

Abstract

Abstract Background Colorectal cancer, one of the most common digestive tumors with high mortality and morbidity worldwide, currently lacks effective therapies available to improve the prognosis. This study was aimed to investigate the potency of Scutellarin against colorectal cancers, and explore the related mechanism via genomic and proteomic analysis. Methods Cell counting kit-8 assay was employed to detect the viability of HCT-116 and RKO cell lines treated with Scutellarin. The apoptosis of HCT-116 and RKO cells after Scutellarin administration was determined by TUNEL staining and Caspase 3/7 activity. Cell cycle was detected by flow cytometry analysis. The wound healing and transwell invasion test detected the role of Scutellarin in migration and invasion of HCT-116 and RKO cells. Meanwhile, the energy metabolism and growth of tumor tissues in vivo at day 28 were observed by PET-CT after Scutellarin administration with 50 mg/kg, 100 mg/kg and 300 mg/kg into 4-week-old nude mice. Blood routine and liver functions were also detected to evaluate the side effect of Scutellarin. Furthermore, the disease and function classifications which the differentially expressed genes and proteins involved after Scutellarin treatment were determined by genomic and proteomic analysis respectively. Results The Scutellarin inhibited the migration and increased apoptosis of HCT-116 and RKO cell lines. Besides, Scutellarin treatment substantially decreased the growth and volume of colorectal tumors in nude mice without side effects on the blood routine and liver function. The differentially expressed genes in RKO cells after Scutellarin administration were mainly enriched in cell death and survival, organismal injury and abnormalities, and cancer. In addition, forty-seven upregulated and twenty-nine downregulated proteins were identified. Functional clustering analysis exhibited enriched biological processes, cellular components, molecular functions and related pathways of these proteins in cellular metabolic. Then protein–protein interactions analysis showed the regulatory relationship among these differentially expressed proteins. Conclusions Taken together, the present findings revealed that Scutellarin exerted significant antitumor effect with no side effects in the blood and liver by regulating various important molecules in tumor proliferation, apoptosis and metastasis.

Keywords

• Colorectal cancer
• Scutellarin
• Antitumor effect
• Genomics, proteomics