| First Author | Zhang X | Year | 2020 |
| Journal | Biosci Rep | Volume | 40 |
| Issue | 12 | PubMed ID | 33245358 |
| Mgi Jnum | J:313929 | Mgi Id | MGI:6801549 |
| Doi | 10.1042/BSR20201006 | Citation | Zhang X, et al. (2020) beta-glucan from Lentinus edodes inhibits breast cancer progression via the Nur77/HIF-1alpha axis. Biosci Rep 40(12) |
| abstractText | BACKGROUND: beta-glucan from Lentinus edodes (LNT) is a plant-derived medicinal fungus possessing significant bioactivities on anti-tumor. Both hypoxia-induced factor-1alpha (HIF)-1alpha and Nur77 have been shown to be involved in the development of breast cancer. However, there is yet no proof of Nur77/HIF-1alpha involvement in the process of LNT-mediated tumor-inhibition effect. METHODS: Immunohistochemistry, immunofluorescence and Hematoxylin-Eosin staining were used to investigate tumor growth and metastasis in MMTV-PyMT transgenic mice. Proliferation and metastasis-associated molecules were determined by Western blotting and reverse transcription-quantitative PCR. Hypoxic cellular model was established under the exposure of CoCl2. Small interference RNA was transfected using Lipofectamine reagent. The ubiquitin proteasome pathway was blunted by adding the proteasome inhibitor MG132. RESULTS: LNT inhibited the growth of breast tumors and the development of lung metastases from breast cancer, accompanied by a decreased expression of HIF-1alpha in the tumor tissues. In in vitro experiments, hypoxia induced the expression of HIF-1alpha and Nur77 in breast cancer cells, while LNT addition down-regulated HIF-1alpha expression in an oxygen-free environment, and this process was in a manner of Nur77 dependent. Mechanistically, LNT evoked the down-regulation of HIF-1alpha involved the Nur77-mediated ubiquitin proteasome pathway. A strong positive correlation between Nur77 and HIF-1alpha expression in human breast cancer specimens was also confirmed. CONCLUSION: Therefore, LNT appears to inhibit the progression of breast cancer partly through the Nur77/HIF-1alpha signaling axis. The findings of the present study may provide a theoretical basis for targeting HIFs in the treatment of breast cancer. |
