Ceritinib (LDK378) prevents bone loss via suppressing Akt and NF-κB-induced osteoclast formation.
Ceritinib (LDK378) prevents bone loss via suppressing Akt and NF-κB-induced osteoclast formation.
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DOI：
10.3389/fendo.2022.939959
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
Ceritinib用于治疗间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）患者，这些患者有发生骨转移的风险。在骨转移过程中，肿瘤细胞释放诱导破骨细胞形成的因子，导致骨质溶解。然而，ceritinib对破骨细胞形成的影响仍不清楚。诱导破骨细胞生成以评估ceritinib对破骨细胞形成和破骨细胞特异性基因表达的影响。蛋白质印迹法用于检查ceritinib对破骨细胞分化作用的分子机制。建立了体内卵巢切除小鼠模型，以验证色瑞替尼在抑制破骨细胞形成和预防骨丢失方面的作用。Ceritinib刺激后，破骨细胞的分化和破骨细胞特异性基因的表达受到抑制。Ceritinib在核因子κ B受体激活剂配体（RANKL）诱导的破骨细胞生成过程中抑制Akt和p65磷酸化。对卵巢切除小鼠给予ceritinib可通过抑制破骨细胞形成改善骨小梁丢失。塞瑞替尼通过抑制破骨细胞Akt和核因子κB（NF-κB）信号传导而有益于预防骨丢失。
Ceritinib is used for the treatment of patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), who are at the risk of developing bone metastasis. During bone metastasis, tumor cells release factors that induce osteoclast formation, resulting in osteolysis. However, the effect of ceritinib on osteoclast formation remains unclear. Osteoclastogenesis was induced to assess the effect of ceritinib on osteoclast formation and osteoclast-specific gene expression. Western blotting was used to examine the molecular mechanisms underlying the effect of ceritinib on osteoclast differentiation. An in vivo ovariectomized mouse model was established to validate the effect of ceritinib in suppressing osteoclast formation and preventing bone loss. The differentiation of osteoclasts and the expression of osteoclast-specific genes were inhibited upon ceritinib stimulation. Ceritinib suppressed Akt and p65 phosphorylation during the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis. The administration of ceritinib to ovariectomized mice ameliorated trabecular bone loss by inhibiting osteoclast formation. Ceritinib is beneficial in preventing bone loss by suppressing osteoclastic Akt and nuclear factor κB (NF-κB) signaling.
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影响因子：
82.9
作者：
Dankbar, Berno;Fennen, Michelle;Pap, Thomas
通讯作者：
Pap, Thomas
影响因子：
37.3
作者：
Della Corte CM;Viscardi G;Di Liello R;Fasano M;Martinelli E;Troiani T;Ciardiello F;Morgillo F
通讯作者：
Morgillo F
影响因子：
4
作者：
Furugaki, Koh;Moriya, Yoichiro;Iwai, Toshiki;Yorozu, Keigo;Yanagisawa, Mieko;Kondoh, Kumiko;Fujimoto-Ohuchi, Kaori;Mori, Kazushige
通讯作者：
Mori, Kazushige
影响因子：
3.8
作者：
Eswaraka J;Giddabasappa A;Han G;Lalwani K;Eisele K;Feng Z;Affolter T;Christensen J;Li G
通讯作者：
Li G
影响因子：
3.6
作者：
Ji, Cheng;Zhang, Li;Ren, Xingcong
通讯作者：
Ren, Xingcong