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姜黄素通过调节MTA1介导的Wnt/β-连环蛋白信号通路抑制非小细胞肺癌的增殖和侵袭。

Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/β-catenin pathway.

作者信息

Lu Yimin, Wei Changjiang, Xi Zhaoqing

机构信息

Department of Emergency, First Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People's Republic of China.

出版信息

In Vitro Cell Dev Biol Anim. 2014 Oct;50(9):840-50. doi: 10.1007/s11626-014-9779-5. Epub 2014 Jun 18.

Abstract

Curcumin, a naturally occurring phenolic compound, has a diversity of antitumor activities. It has been previously demonstrated that curcumin can inhibit the invasion and metastasis of tumors through activation of the tumor suppressor DnaJ-like heat shock protein 40 (HLJ1). However, the specific roles and mechanisms of curcumin in regulating the malignant behaviors of non-small cell lung cancer (NSCLC) cells still remain unclear. In this study, we found that curcumin could inhibit the proliferation and invasion of NSCLC cells and induce G0/G1 phase arrest. Metastasis-associated protein 1 (MTA1) overexpression has been detected in a wide variety of aggressive tumors and plays an important role on cell invasion and metastasis. Our results showed that curcumin could effectively inhibit the MTA1 expression of NSCLC cells. Further research on the subsequent mechanism showed that curcumin inhibited the proliferation and invasion of NSCLC cells through MTA1-mediated inactivation of Wnt/β-catenin pathway. Wnt/β-catenin signaling was reported to play a critical cooperative role on promoting lung tumorigenesis. Thus, these investigations provided novel insights into the mechanisms of curcumin on inhibition of NSCLC cell growth and invasion and showed potential therapeutic strategies for NSCLC.

摘要

姜黄素是一种天然存在的酚类化合物,具有多种抗肿瘤活性。先前已证明姜黄素可通过激活肿瘤抑制因子DnaJ样热休克蛋白40(HLJ1)来抑制肿瘤的侵袭和转移。然而,姜黄素在调节非小细胞肺癌(NSCLC)细胞恶性行为中的具体作用和机制仍不清楚。在本研究中,我们发现姜黄素可抑制NSCLC细胞的增殖和侵袭并诱导G0/G1期阻滞。转移相关蛋白1(MTA1)在多种侵袭性肿瘤中均有过表达,且在细胞侵袭和转移中起重要作用。我们的结果表明,姜黄素可有效抑制NSCLC细胞中MTA1的表达。对后续机制的进一步研究表明,姜黄素通过MTA1介导的Wnt/β-连环蛋白信号通路失活来抑制NSCLC细胞的增殖和侵袭。据报道,Wnt/β-连环蛋白信号在促进肺癌发生中起关键协同作用。因此,这些研究为姜黄素抑制NSCLC细胞生长和侵袭的机制提供了新的见解,并展示了NSCLC潜在的治疗策略。

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