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NPS - 2143(盐酸盐)可抑制黑色素瘤癌细胞增殖,并诱导自噬和凋亡。

NPS - 2143 (hydrochloride) inhibits melanoma cancer cell proliferation and induces autophagy and apoptosis.

作者信息

Wang Shumei, Qiu Liyun, Song Haiyan, Dang Ningning

机构信息

Department of Community Medicine, Jinan Central Hospital affiliated to Shandong University, No.105 Jiefang Road, Jinan 250013, Shandong Province, China.

Department of Pharmacy, Jinan Central Hospital affiliated to Shandong University, No.105 Jiefang Road, Jinan 250013, Shandong Province, China.

出版信息

Med Sci (Paris). 2018 Oct;34 Focus issue F1:87-93. doi: 10.1051/medsci/201834f115. Epub 2018 Nov 7.

Abstract

Melanoma is a common and aggressive skin cancer caused by the oncogenic transformation of melanocytes. NPS-2143 (hydrochloride) is a calcification drug that acts as an antagonist of the calcium-sensing receptor (CaSR) and consequently stimulates the release of parathyroid hormone. In the present work, we treated cells from the human melanoma cell line M14 to investigate the effects of NPS-2143 on melanoma cells and elucidate their underlying mechanisms. We observed that NPS-2143 inhibits the survival and proliferation of M14 cells and suppresses the migration and proliferation of M14 cells by inducing apoptosis. The Bax/Bcl‑2 ratio in M14 cells was enhanced by the NPS-2143 treatment, suggesting that the mitochondrial apoptotic pathway was activated. The expression and phosphorylation of proteins involved in the PI3K signaling pathway were altered by NPS-2143 treatment. Our data show that NPS-2143 impacts the viability and induces the apoptosis of melanoma M14 cells through its impact on the PI3K signaling pathway. It suggests that NPS-2143 could represent a promising candidate for melanoma treatment.

摘要

黑色素瘤是一种常见且侵袭性强的皮肤癌,由黑素细胞的致癌转化引起。NPS - 2143(盐酸盐)是一种钙化药物,作为钙敏感受体(CaSR)的拮抗剂,从而刺激甲状旁腺激素的释放。在本研究中,我们用人类黑色素瘤细胞系M14的细胞进行处理,以研究NPS - 2143对黑色素瘤细胞的影响并阐明其潜在机制。我们观察到NPS - 2143抑制M14细胞的存活和增殖,并通过诱导凋亡抑制M14细胞的迁移和侵袭。NPS - 2143处理可提高M14细胞中的Bax/Bcl - 2比值,表明线粒体凋亡途径被激活。NPS - 2143处理改变了PI3K信号通路中相关蛋白的表达和磷酸化。我们的数据表明,NPS - 2143通过影响PI3K信号通路影响黑色素瘤M14细胞的活力并诱导其凋亡。这表明NPS - 2143可能是黑色素瘤治疗的一个有前景的候选药物。

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