Affiliation:
1. Department of Dermatology , Jinan Central Hospital affiliated to Shandong University , Jinan 250013, Shandong Province , P.R. China
2. The First Clinical Medical College of Lanzhou University , Lanzhou 730000, Gansu Province , P.R. China
3. Department of Neurobiology , Key Laboratory of Medical Neurobiology, School of Medicine, Shandong University , Jinan 250012, Shandong Province , P.R. China
Abstract
Abstract
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.
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