School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
Shaanxi Provincial People's Hospital, Xi'an, 710068, P.R. China.
Curr Cancer Drug Targets. 2022;22(4):328-339. doi: 10.2174/1568009622666220225121009.
Cutaneous T cell lymphoma (CTCL) is a kind of extranodal non-Hodgkin Tcell lymphoma without healable treatment in the clinic. JAK2 amplification in CTCL patients makes it a potential target for CTCL treatment. In the present study, we aimed to evaluate the anticancer effect of ND-16, a novel nilotinib derivate, on CTCL cells and the underlying mechanism targeting JAK2.
We found that ND-16 was capable of regulating JAK2 and had a selective inhibitory effect on CTCL H9 cells. The surface plasmon resonance and molecular docking study indicated ND-16 bound to JAK2 with a high binding affinity. Further investigation revealed that ND-16 inhibited the downstream cascades of JAK2, including STATs, PI3K/AKT/mTOR, and MAPK pathways, followed by regulation of Bcl-2 family members and cell cycle proteins CDK/- Cyclins. Flow cytometry analysis confirmed these results that ND-16-treated H9 cells showed cell apoptosis and cell cycle arrest at S-phase.
ND-16 may be of value in a potential therapy for the management of CTCL.
皮肤 T 细胞淋巴瘤（CTCL）是一种结外非霍奇金 T 细胞淋巴瘤，临床上尚无治愈方法。CTCL 患者存在 JAK2 扩增，使其成为 CTCL 治疗的潜在靶点。本研究旨在评估新型尼罗替尼衍生物 ND-16 对 CTCL 细胞的抗癌作用及其针对 JAK2 的潜在作用机制。
我们发现 ND-16 能够调节 JAK2，并对 CTCL H9 细胞具有选择性抑制作用。表面等离子体共振和分子对接研究表明，ND-16 与 JAK2 具有高结合亲和力。进一步研究表明，ND-16 抑制了 JAK2 的下游级联反应，包括 STATs、PI3K/AKT/mTOR 和 MAPK 通路，随后调节 Bcl-2 家族成员和细胞周期蛋白 CDK/-Cyclins。流式细胞术分析证实，ND-16 处理的 H9 细胞表现出细胞凋亡和 S 期细胞周期停滞。
ND-16 可能对 CTCL 的治疗管理具有价值。
