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JTC-801通过PI3K-Akt-mTOR信号通路抑制黑色素瘤细胞生长。

JTC-801 Suppresses Melanoma Cells Growth through the PI3K‑Akt‑mTOR Signaling Pathways.

作者信息

Li Jing, Huang Fei

机构信息

School of Medicine, Shandong University, Jinan, Shandong, P.R. China - Department of Dermatology, Shandong Provincial Third Hospital, Jinan, Shandong, P.R. China.

Department of Dermatology, Yucheng People's Hospital, No.753, Kaituo Road, Yu Town, Yucheng 251200, Shandong, P.R. China.

出版信息

Med Sci (Paris). 2018 Oct;34 Focus issue F1:8-14. doi: 10.1051/medsci/201834f102. Epub 2018 Nov 7.

Abstract

Melanoma is considered as one of the most potentially fatal and aggressive malignancies. Due to the limited efficacy or drug resistance of the current targeted therapies of melanoma, developing new therapeutic drugs against new targets to effectively control tumor growth is greatly needed. In this study, the effect of JTC-801, a selective small-molecule antagonist of nociceptin receptor and analgesic agent, on a melanoma cell line, M14, has been studied. We demonstrate herein that JTC-801 could efficiently suppress the proliferation, migration and invasion capacity of the M14 melanoma cells, and induced a strong apoptosis. Importantly, our results provide the underlying molecular mechanism of these effects. JTC-801 cells regulate M14 cells by inhibiting the PI3K-Akt‑mTOR pathway. These results suggest that JTC-801 should be further studied in preclinical modes to establish whether it represents a potential small anticancer candidate drug against melanoma.

摘要

黑色素瘤被认为是最具潜在致命性和侵袭性的恶性肿瘤之一。由于目前黑色素瘤靶向治疗的疗效有限或存在耐药性,迫切需要开发针对新靶点的新型治疗药物以有效控制肿瘤生长。在本研究中,对一种选择性的孤啡肽受体小分子拮抗剂及镇痛药JTC - 801对黑色素瘤细胞系M14的作用进行了研究。我们在此证明,JTC - 801能够有效抑制M14黑色素瘤细胞的增殖、迁移和侵袭能力,并诱导强烈的细胞凋亡。重要的是,我们的结果提供了这些作用的潜在分子机制。JTC - 801细胞通过抑制PI3K - Akt - mTOR途径来调节M14细胞。这些结果表明,JTC - 801应在临床前模式下进一步研究,以确定它是否代表一种潜在的抗黑色素瘤小分子抗癌候选药物。

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