Melanoma is the most aggressive, therapy-resistant skin cancer. The mammalian target of rapamycin (mTOR), the serine/threonine kinase which integrates both intracellular and extracellular signals, plays a crucial role in coordinating the balance between the growth and death of cells. The object of this study is a comparison of the influence of mTOR inhibitor everolimus in the concentration range between 20 nM and 10 μM, used individually and in combination with selected downstream protein kinases inhibitors: LY294002 (PI3K), U0126 (ERK1/2), AS-703026 (MEK) and MK-2206 (AKT) on the expression of pro-survival proteins: p-Bcl-2 (S70), p-Bcl-2 (T56), Bcl-2, Bcl-xL, Mcl-1, activity of caspase-3, proliferation and induction of apoptosis in melanoma cells. Current results clearly show that the nanomolar concentration of the mTOR inhibitor everolimus in combination with the inhibitor of MAP kinase (AS-703026) or AKT kinase (MK-2206) is effective in inducing apoptosis and reducing proliferation of melanoma cells. The herein research results confirm the hypothesis on the important role of mTOR signaling in cancer progression, and gives hope that implementation of successful combination of its inhibitors will find recognition and application in cancer treatment in the near future.

中文翻译：

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mTOR抑制剂依维莫司诱导黑色素瘤细胞凋亡。

黑色素瘤是最具有侵略性，抗药性的皮肤癌。雷帕霉素（mTOR）的哺乳动物靶标是整合细胞内和细胞外信号的丝氨酸/苏氨酸激酶，在协调细胞生长与死亡之间的平衡中起着至关重要的作用。这项研究的目的是比较mTOR抑制剂依维莫司在20 nM至10μM浓度范围内的影响，这些影响单独使用，并与选定的下游蛋白激酶抑制剂组合使用：LY294002（PI3K），U0126（ERK1 / 2）， AS-703026（MEK）和MK-2206（AKT）对存活蛋白的表达：p-Bcl-2（S70），p-Bcl-2（T56），Bcl-2，Bcl-xL，Mcl- 1，caspase-3的活性，黑色素瘤细胞的增殖和凋亡的诱导。当前结果清楚地表明，mTOR抑制剂依维莫司的纳摩尔浓度与MAP激酶（AS-703026）或AKT激酶（MK-2206）的抑制剂结合可有效诱导细胞凋亡和减少黑色素瘤细胞的增殖。本文的研究结果证实了关于mTOR信号在癌症进展中的重要作用的假设，并希望成功实施其抑制剂的组合将在不久的将来获得癌症的认识和应用。