Uvea melanomu hücre dizilerinde AMPK modülasyonunun hücre proliferasyonuna etkisinin incelenmesi

Abstract

The aim of this study is to comparatively determine the accurate strategy regarding AMPK targeting by analyzing the cell proliferation response of uveal melanoma cell lines to AMPK activation and/or inhibition. Uveal melanoma is the most common primary intraocular malignant tumor. AMPK plays an important role in the transformation of a healthy cell into a tumor cell and tumor progression by providing metabolic adaptation. AMPK can have a tumor suppressor or a protooncogenic impact under different circumstances. In our study, uveal melanoma cell lines MEL270, OMM2.5, 92.1 and MP46, were incubated separately with varying doses of AMPK activator (A-769662) or inhibitor (Dorsomorphin) agents. MTT cell proliferation assays, the 24-hour rates of proliferation were determined and 92.1 cells showed the highest proliferation rate (92.1, MP46, OMM2.5, MEL270 in the decreasing order). There was no correlation between the cell proliferation rates and the proliferation responses to the different drug groups. The responses of cell lines to these AMPK modulating agents were determined by XTT cell proliferation assays after a 48-hour incubation. There was a decrease in cell proliferation response in all cell lines incubated with AMPK activator, compared to the control group of the corresponding cell lines which were not exposed to any agents. There was no correlation between the amount of decrease in cell proliferation and dosage increment in any of the cell lines. In MP46 cell line, the cell proliferation was found to be higher as a result of the treatment of AMPK activator in increasing doses over 50 μM. The response of all cell lines to the treatment of AMPK inhibitor was observed significantly, as cell proliferations declined further with the increasing doses over 5 μM.