Zhou Kairui, Shi Xiaoli, Huo Jinling, Liu Weihua, Yang Dongxiao, Yang Tengjiao, Qin Tiantian, Wang Cong
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Int J Biol Macromol. 2017 Aug;101:427-437. doi: 10.1016/j.ijbiomac.2017.03.064. Epub 2017 Mar 16.
Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β 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.
耐药性和转移显著阻碍癌症化疗并恶化预后。骨形态发生蛋白4（BMP4）属于转化生长因子-β超家族，在细胞增殖和软骨分化中具有广泛的生物学活性，并且还能够诱导迁移和侵袭。在此，我们研究了BMP4在耐紫杉醇的人食管癌EC109细胞（EC109/Taxol）和耐多西他赛的人胃癌MGC803细胞（MGC/Doc）转移调控中的作用。在这些耐药细胞系中，我们发现相对于各自的亲本细胞系，细胞运动性增强且BMP4上调。与体外实验一致，EC109/Taxol裸鼠的迁移潜能和BMP4表达增加。此外，为了探究BMP4是否是增强EC109/Taxol细胞转移所必需的，使用了BMP信号通路的药理学抑制剂 dorsomorphin；同时，我们发现迁移和侵袭能力受到抑制。此外，还研究了经典的Smad信号通路。总体而言，我们的研究表明BMP4参与EC109/Taxol细胞的侵袭和迁移调控，抑制BMP4可能是癌症治疗中干扰转移的一种新策略。
