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Published on: August 23, 2024
MDA-19 Suppresses Progression of Melanoma Via Inhibiting the PI3K/Akt Pathway
Ningning Dang1, Xianguang Meng1, Shanshan Ma1
1Department of Dermatology, Jinan Central Hospital affiliated to Shandong University, Jinan 250013, Shandong Province, P.R. China.
Objective:
To investigate the effect of MDA-19 on progression of melanoma, and explore the relevant mechanism.
Methods:
The melanoma cell lines, M14 and UACC257, were treated with different concentrations of MDA-19, then CCK8, clone formation assay, Transwell and flow cytometry assays were performed to examine cell proliferation, migration, invasion and apoptosis, respectively. The expression of apoptosis-related proteins (Bcl-2, Bax and caspase 3 P17), EMT and signaling pathway-related proteins were also detected by Western blot.
Results:
MDA-19 inhibited melanoma cells in a dose-dependent manner. Compared to the NC group, MDA-19 significantly inhibited cell growth capacity, migration and invasion of M14 and UACC257 cells, and accelerated cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax and Caspase 3 in M14 and UACC257 cells. Moreover, MDA-19 was observed to up-regulate the expression of E-cad and down-regulate the expression of N-cad, Vimentin and Slug in melanoma cells in vitro. Furthermore, MDA-19 could inhibit the PI3K/Akt pathway by blocking Akt phosphorylation (p-Akt) and downstream proteins, P70 and Cyclin D1 in M14 and UACC257 cells.
Conclusion:
Our data demonstrate that MDA-19 could inhibit progression of melanoma by suppressing the PI3K/Akt pathway, suggesting that MDA-19 is a potential anti-cancer agent for therapy of melanoma.
Insights
MDA-19 effectively inhibits melanoma progression by reducing cell growth, migration, and invasion. This compound also promotes apoptosis and suppresses the PI3K/Akt pathway, indicating its potential as a melanoma therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Melanoma is an aggressive skin cancer with limited treatment options.
- Understanding novel therapeutic targets is crucial for effective melanoma treatment.
Purpose of the Study:
- To investigate the anti-melanoma effects of MDA-19.
- To elucidate the underlying molecular mechanisms of MDA-19 action.
Main Methods:
- Melanoma cell lines (M14, UACC257) were treated with MDA-19.
- Assays included CCK8, clone formation, Transwell, and flow cytometry.
- Protein expression of apoptosis, EMT, and signaling pathway markers was analyzed via Western blot.
Main Results:
- MDA-19 demonstrated dose-dependent inhibition of melanoma cell proliferation, migration, and invasion.
- Apoptosis was induced via the mitochondrial pathway, regulating Bcl-2/Bax and Caspase 3.
- MDA-19 modulated epithelial-mesenchymal transition (EMT) markers (E-cad, N-cad, Vimentin, Slug).
- The PI3K/Akt pathway was inhibited by blocking Akt phosphorylation and downstream targets (P70, Cyclin D1).
Conclusions:
- MDA-19 inhibits melanoma progression by suppressing the PI3K/Akt signaling pathway.
- MDA-19 shows potential as an anti-cancer agent for melanoma therapy.
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