Background
Melanoma is a highly malignant and difficult-to-treat skin cancer. Many researchers are exploring natural products for its treatment. Lentinan (LNT), extracted from Lentinus edodes, exerts strong anti-tumor effects. In this study, we aimed to establish a new approach for melanoma treatment by analyzing the pharmacological properties of LNT.
Conclusion
Overall, LNT inhibited tumor growth and promoted apoptosis by regulating the AKT/Nur77/Bcl-2 pathway in melanoma cells. Our findings highlight the potential of LNT for drug development and clinical treatment of melanoma.
Methods
A tumor-bearing mouse model was established to assess tumor growth. Cell survival was analyzed using the cell counting kit-8 assay. Molecular localization and expression were assessed via western blotting, histological staining, and cell staining.
Results
LNT significantly inhibited the growth and proliferation of melanoma cells. In vitro, LNT inhibited the proliferation of B16F10 cells. It also decreased the expression levels of the proliferation-related molecules, poly (ADP ribose) polymerase 1 and proliferating cell nuclear antigen, in B16F10 murine melanoma cells. Moreover, LNT decreased the expression of the orphan nuclear receptor, Nur77, but increased that of the apoptosis-related protein, Bcl-2. LNT promoted the interaction between nuclear receptor Nur77 and mitochondrial apoptosis-associated protein Bcl-2, thereby inducing apoptosis in melanoma cells. Small-interfering RNA-mediated Nur77 knockdown revealed that LNT promoted melanoma cell apoptosis via the Nur77/Bcl-2 pathway. Furthermore, AKT played key roles in the cell apoptosis-inducing and anti-tumor effects of LNT via the Nur77/Bcl-2 pathway.