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14 November 2019 : Laboratory Research  

Sonidegib, a Smoothened Inhibitor, Promotes Apoptosis and Suppresses Proliferation of Natural Killer/T-Cell Lymphoma

Shengquan Liu1ABCDEF, Chuntuan Li1A, Pengliang Xin1B, Yan Zheng1C, Qunyi Peng1D, Yahong Xu1E, Ying Luo1F, Yishen Wu1F, Xiongpeng Zhu1AG*

DOI: 10.12659/MSM.918812

Med Sci Monit 2019; 25:8579-8586

Abstract

BACKGROUND: Dysregulation of the Hedgehog (Hh) pathway modulates various aspects of hematologic and solid tumors, but its effects in human Natural killer/T-cell lymphoma (NKTCL) are unclear. Moreover, no study has examined the consequences of pharmacologically inhibiting Hh signaling in NKTCL cell lines.

MATERIAL AND METHODS: In this study, the expression of Smoothened (Smo) and Glioma-associated oncogene 1 (Gli1) in NKTCL tissue were scrutinized. Two human NKTCL cell lines, SNK6 and SNT8, were subjected to various doses of sonidegib (a Smo inhibitor) and incubated for distinct durations. The cell apoptosis was examined by flow cytometry, CCK-8 assay was run to assess proliferation, and protein levels were quantified by Western blotting.

RESULTS: Both Smo and Gli1 expression were higher in NKTCL tissue than in Lymphoid Reactive Hyperplasia (LRH). Sonidegib significantly suppressed proliferation in NKTCL cells and the effect was dose-dependent. Further analysis revealed that sonidegib treatment elevated the number of apoptotic cells in a dose- and time-dependent manner. In addition, sonidegib downregulated Smo and Gli1expression in NKTCL cells.

CONCLUSIONS: The Hh pathway is crucial to the development of NKTCL and thus holds huge promise as a treatment for this disease.

Keywords: Hedgehogs, Natural Killer T-Cells, Biphenyl Compounds, Hedgehog Proteins, Lymphoma, T-Cell, Smoothened Receptor, Zinc Finger Protein GLI1

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750