UNBS5162 and amonafide inhibits tumor progression in human melanoma by the AKT/mTOR pathway
Authors Ye Y, Huang S, Wu Y
Received 19 June 2018
Accepted for publication 25 January 2019
Published 22 March 2019 Volume 2019:11 Pages 2339—2348
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Nakshatri
Yingyi Ye,1 Shuhong Huang,2 Yingying Wu3
1Department of Dermatology, HwaMei Hospital, University of Chinese Academy of Sciences, Zhejiang, China; 2Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Basic Medical Science, Shandong University, Shandong, China; 3Department of Oncology, HwaMei Hospital, University of Chinese Academy of Sciences, Zhejiang, China
Background: Human 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.
Methods: Cell 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.
Results: In 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 dosedependent 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.
Conclusion: These 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.
Keywords: cell apoptosis, proliferation, M14, A375, epithelial-mesenchymal transition
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