Identification of molecular anti-metastasis mechanisms of lycorine in colorectal cancer by RNA-seq analysis
| Autor: | Chaojie Wang, Chaochao Ge, Songqiang Xie, Kemeng Zhang, Fujun Dai, Xiaojuan Xu, Lei Gao, Xinna Li, Yongli Feng, Senzhen Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Pharmaceutical Science Apoptosis Biology 03 medical and health sciences chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Annexin Cell Line Tumor Drug Discovery Animals Humans MTT assay Propidium iodide RNA-Seq Neoplasm Metastasis Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Cell Proliferation Pharmacology 0303 health sciences Mice Inbred BALB C Kinase Wnt signaling pathway Lycorine Endoplasmic Reticulum Stress Phenanthridines Complementary and alternative medicine chemistry 030220 oncology & carcinogenesis Cancer research Amaryllidaceae Alkaloids Molecular Medicine Colorectal Neoplasms Signal Transduction |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 85 |
| ISSN: | 1618-095X |
| Popis: | Background Colorectal cancer (CRC) is one of the most common malignancies worldwide. Metastasis is the major cause of death in patients with CRC. Lycorine, the phenanthridine alkaloid most commonly found in spp of the Amaryllidaceae family, has shown promising anticancer activities with minor side effects. However, the effects and the detailed mechanism of lycorine against metastasis of CRC remains unclear. Study design/methods The purpose of this study was to investigate the effects of lycorine on CRC and characterize the molecular mechanisms observed in lycorine-treated CRC cells using RNA-sequencing. MTT assay, colony formation assay, acridine orange/ethidium bromide (AO/EB) staining and Annexin V-FITC/Propidium iodide (PI) staining were conducted to examine the effects of lycorine on cell proliferation and apoptosis in CRC cells. RNA sequencing, real-time PCR assays and western blot were performed. Migration and invasion abilities of lycorine-treated CRC cells were investigated by wound healing and transwell invasion assays. The mouse CRC lung metastasis model was established and was used to detect the effect of lycorine on CRC in vivo. Results Our results demonstrated that lycorine inhibited the proliferation and colony formation of CRC cells in a concentration-dependent manner. AO/EB staining and Annexin V-FITC/PI staining showed that lycorine induced apoptosis in a concentration-dependent manner. Lycorine also reduced lung metastasis of CRC in vivo. Moreover, transcriptomic analysis suggested that lycorine regulated the expression of 3556 genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was implicated according to the differentially expressed genes (DEGs), and multiple pathways including those of mitogen-activated protein kinase (MAPK), relaxin, Ras, phosphatidylinositol 3‑kinase (PI3K)-protein kinase B (Akt) and Wnt/β-catenin were selected by functional enrichment analyses. Furthermore, based on transcriptomic analysis, we found that the tumor necrosis factor (TNF) pathway and endoplasmic reticulum stress were responsible for lycorine-induced apoptosis. Conclusions These results obtained in this study demonstrated that lycorine has the potential to suppress CRC in vitro and in vivo through the lycorine-regulated multiple signaling pathways. |
| Databáze: | OpenAIRE |
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