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Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent signaling pathway

机译:姜黄素通过依赖Rac1的信号通路抑制肺癌细胞的迁移和侵袭

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Curcumin, a natural and crystalline compound isolated from the plant Curcuma longa with low toxicity in normal cells, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about antimetastasis effects and mechanism of curcumin in lung cancer. Rac1 is an important small Rho GTPases family protein and has been widely implicated in cytoskeleton rearrangements and cancer cell migration, invasion and metastasis. In this study, we examined the influence of curcumin on in vitro invasiveness of human lung cancer cells and the expressions of Rac1. The results indicate that curcumin at 10 mu M slightly reduced the proliferation of 801D lung cancer cells but showed an obvious inhibitory effect on epidermal growth factor or transforming growth factor beta 1-induced lung cancer cell migration and invasion. Meanwhile, we demonstrated that the suppression of invasiveness correlated with inhibition of Rac1/PAK1 signaling pathways and matrix metalloproteinase (MMP) 2 and 9 protein expression by combining curcumin treatment with the methods of Rod gene silence and overexpression in lung cancer cells. Laser confocal microscope also showed that Rac1-regulated actin cytoskeleton rearrangement may be involved in anti-invasion effect of curcumin on lung cancer cell. At last, through xenograft experiments, we confirmed the connection between Rac1 and the growth and metastasis inhibitory effect of curcumin in vivo. In summary, these data demonstrated that low-toxic levels of curcumin could efficiently inhibit migration and invasion of lung cancer cells through inhibition of Rac1/PAK1 signaling pathway and MMP-2 and MMP-9 expression, which provided a novel insight into the molecular mechanism of curcumin against lung cancer. (C) 2014 Elsevier Inc. All rights reserved.
机译:姜黄素是从植物姜黄中分离出的天然结晶化合物,对正常细胞毒性低,已被证明可以防止癌变并防止肿瘤的发展。然而,关于姜黄素在肺癌中的抗转移作用和作用机制知之甚少。 Rac1是重要的小Rho GTPases家族蛋白,已广泛参与细胞骨架重排以及癌细胞迁移,侵袭和转移。在这项研究中,我们检查了姜黄素对人肺癌细胞体外侵袭性和Rac1表达的影响。结果表明,姜黄素在10μM时会稍微降低801D肺癌细胞的增殖,但对表皮生长因子或转化生长因子β1诱导的肺癌细胞迁移和侵袭具有明显的抑制作用。同时,我们证明姜黄素治疗与Rod基因沉默和过度表达的方法相结合,可以抑制侵袭性,抑制Rac1 / PAK1信号通路和基质金属蛋白酶(MMP)2和9蛋白的表达。激光共聚焦显微镜还显示,Rac1调节的肌动蛋白细胞骨架重排可能与姜黄素对肺癌细胞的抗侵袭作用有关。最后,通过异种移植实验,我们证实了Rac1与姜黄素在体内的生长和转移抑制作用之间的联系。总之,这些数据表明低毒性姜黄素可以通过抑制Rac1 / PAK1信号通路以及MMP-2和MMP-9表达来有效抑制肺癌细胞的迁移和侵袭,从而为分子机制提供了新的见解。姜黄素抗肺癌。 (C)2014 Elsevier Inc.保留所有权利。

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