OBJECTIVE To investigate the role and mechanism of phellopterin in preventing breast cancer metastasis. METHODS The cytotoxicity of phellopterin was evaluated by CCK-8 assay and flow cytometry for cell cycle and apoptosis. The effect of phellopterin on the adhesion between cancer cells and vascular endothelial cells was detected by immunofluorescence. The effect of phellopterin on the expression of cell adhesion molecules (CAMs) on the surface of HUVECs was detected by flow cytometry. The effect of phellopterin on the expression of epithelial-mesenchymal transition(EMT) regulatory proteins in cancer cells was detected by Western blot and quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR). The inhibitory effect of phellopterin on lung metastasis of breast cancer in mice was evaluated by a mouse cancer metastasis model. RESULTS Phellopterin exhibits relatively low cytotoxicity and can inhibit the adhesion of cancer cells to HUVECs by reducing the expression of CAMs, such as vascular cell adhesion molecule-1(VCAM-1), intercellular cell adhesion molecule-1(ICAM-1), and E-selectin, which are induced by the inflammatory factor TNF-α. Additionally, phellopterin suppresses the expression of regulatory factors associated with EMT transformation and metastasis-promoting proteins, including tripartite motif containing 22(TRIM22), thrombospondin-1(THBS1), and KIT ligand(KITLG). In a mouse model of cancer metastasis, phellopterin was shown to significantly inhibit breast cancer lung metastasis and enhance the activity of anti-tumor immune cells (cytotoxic T lymphocytes and natural killer cells) in peripheral blood. CONCLUSION Phellopterin shows a significant preventive effect on breast cancer metastasis and holds substantial potential for further development and application.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |