UNBS5162 and amonafide inhibits tumor progression in human melanoma by the AKT/mTOR pathway.

Abstract

BackgroundHuman melanoma is a malignant tumor originated from melanocytes with high invasion, metastasis, and poor prognosis. In this study, the effects of naphthalimides UNBS5162 and amonafide on the properties of proliferation and apoptosis in human melanoma cells were confirmed.MethodsCell proliferation was determined by CCK8 and clone formation assay. Transwell assay was performed to detect the migration and invasion of M14 and A375 cells. Cell apoptosis was estimated using flow cytometry.ResultsIn a drug sensitivity assay, cell viability decreased with increasing concentrations of UNBS5162 or amonafide. Likewise, proliferation of M14 or A375 cells treated with 10 μM UNBS5162 or 8 μM amonafide decreased significantly when compared with negative control (NC) cells, their inhibition effect verified by means of a clone formation assay. After the treatment with UNBS5162 or amonafide, the migration of melanoma cells was inhibited in a dosede-pendent manner. The number of invaded cells treated with UNBS5162 was also significantly reduced when compared with those of the NC cells. The apoptotic cell numbers treated with UNBS5162 or amonafide decreased significantly when compared with the M14 and A375 cells in the NC group. According to Western blot results, phosphorylation of AKT and expressions of mesenchymal marker factors were inhibited in cells treated with UNBS5162 or amonafide.ConclusionThese results reveal that UNBS5162 inhibits the cell activity of melanoma cells through the AKT/mTOR signaling pathway, and reverses epithelial–mesenchymal transition conversion in human melanoma cells. This study on UNBS5162 and amonafide in melanomas provides an experimental basis of their uses and potential value on human melanoma treatment.