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Fbxo6 通过抑制非小细胞肺癌中 Chk1 的激活赋予顺铂药物敏感性。

Fbxo6 confers drug-sensitization to cisplatin via inhibiting the activation of Chk1 in non-small cell lung cancer.

机构信息

Department of Pathology, The First Affiliated Hospital and the Basic Medical Sciences of China Medical University, Shenyang, China.

Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

FEBS Lett. 2019 Jul;593(14):1827-1836. doi: 10.1002/1873-3468.13461. Epub 2019 Jun 7.

Abstract

Fbxo6 (also called FBG2) is a critical component of the evolutionarily conserved ubiquitin-protein ligase complex SCF (Skp1/Cdc53-Cullin1/F-box). Previous studies have demonstrated that Fbxo6 facilitates the growth and proliferation but inhibits the apoptosis and invasion of gastric cancer cells. However, the role of Fbxo6 in non-small cell lung cancer (NSCLC) is still not clear. Our results revealed that Fbxo6 expression is correlated with early TNM stage and favorable overall survival of NSCLC patients. Further in vitro experiments showed that Fbxo6 inhibits proliferation, facilitates apoptosis and promotes the sensitivity of cisplatin via decreased expression and phosphorylation of Chk1. Thus, Fbxo6 may be a useful prognosis marker and therapeutic target to overcome the chemoresistance of cisplatin-based chemotherapy agents in NSCLC patients.

摘要

Fbxo6(也称为 FBG2)是进化上保守的泛素-蛋白连接酶复合物 SCF(Skp1/Cdc53-Cullin1/F-box)的关键组成部分。先前的研究表明,Fbxo6 促进胃癌细胞的生长和增殖,但抑制其凋亡和侵袭。然而,Fbxo6 在非小细胞肺癌(NSCLC)中的作用尚不清楚。我们的研究结果表明,Fbxo6 的表达与 NSCLC 患者的早期 TNM 分期和良好的总生存率相关。进一步的体外实验表明,Fbxo6 通过降低 Chk1 的表达和磷酸化来抑制增殖、促进凋亡并增加顺铂的敏感性。因此,Fbxo6 可能是一种有用的预后标志物和治疗靶点,可克服 NSCLC 患者基于顺铂的化疗药物的耐药性。

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