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首页> 外文期刊>International Journal of Biological Macromolecules: Structure, Function and Interactions >Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells
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Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells

机译:骨形态发生蛋白4在过表达并促进抗药性癌细胞的迁移和侵袭

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Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-beta superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc). In these drug-resistant cell lines, we found the cell motility was enhanced and BMP4 was up-regulated relative to their respective parental cell lines. Consistent with in vitro assays, migration potential and BMP4 expression were increased in EC109/Taxol nude mice. Furthermore, to address whether BMP4 was required to enhance the metastatic in EC109/Taxol cells, the pharmacological inhibitor of BMP signaling dorsomorphin was used; meanwhile, we found that the migration and invasion abilities were inhibited. Moreover, the canonical Smad signaling pathway was investigated. Overall, our studies demonstrated that BMP4 participates in the regulation of invasion and migration by EC109/Taxol cells, and inhibition of BMP4 may be a novel strategy to interfere with metastasis in cancer therapy. (C) 2017 Elsevier B.V. All rights reserved.
机译:耐药性和转移显着妨碍化疗和恶化癌症预后。骨形态发生蛋白4(BMP4)属于TGF-Beta超家族,具有较广泛的细胞增殖和软骨分化的生物活性,并且也能够诱导迁移和侵袭。在此,我们研究了BMP4在紫杉醇抗性人食管癌EC109细胞(EC109 / TAXOL)和多西紫杉醇抗性人胃癌MGC803细胞(MGC / DOC)中的调节中的作用。在这些耐药细胞系中,我们发现细胞活性增强,并且BMP4相对于其各自的亲本细胞系上调。 EC109 / Taxol裸鼠中,迁移电位和BMP4表达一致,迁移电位和BMP4表达一致。此外,为了解决BMP4是否需要增强EC109 /紫杉醇细胞中的转移,使用BMP信号传导背体的药理学抑制剂;同时,我们发现迁移和侵袭能力受到抑制。此外,研究了规范的Smad信号通路。总体而言,我们的研究表明,BMP4参与EC109 /紫杉醇细胞的侵袭和迁移,并且BMP4的抑制可能是干扰癌症治疗中转移的新策略。 (c)2017年Elsevier B.V.保留所有权利。

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