Han Rongfei, Xiong Jie, Xiao Ruijing, Altaf Ehtisham, Wang Jin, Liu Yanping, Xu Hui, Ding Qianshan, Zhang Qiuping
Department of Immunology, Wuhan University School of Basic Medical Science, Dong Hu Road 185, Wuchang, Wuhan, Hubei, 430071, People's Republic of China.
Tumour Biol. 2013 Feb;34(1):277-84. doi: 10.1007/s13277-012-0548-3. Epub 2012 Oct 10.
The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms and has recently been implicated in promoting carcinoma invasion and metastasis. Besides their therapeutic effects, accumulating evidences suggest that chemotherapeutic agents also induced EMT and enhanced the malignancy of treated cancer cells; however, the mechanism(s) still remains unclear. Here, we investigated the role of β-catenin signaling in doxorubicin (Dox)-induced EMT in human gastric cancer cell line BGC-823. We found that the transient treatment of Dox induced EMT and enhanced the in vitro migration ability of cancer cells. We also found that β-catenin signaling was activated upon Dox treatment. Inhibition of β-catenin by indomethacin (Indo) or siRNA suppressed Dox-induced EMT and decreased cancer cell migration ability. Our results showed that β-catenin signaling was critical to Dox-induced EMT. Indo and other β-catenin inhibitors may have a potential implication in prevention of gastric cancer metastasis.
上皮-间质转化（EMT）是多细胞生物体中控制形态发生的一个基本过程，最近被认为与促进癌侵袭和转移有关。除了其治疗作用外，越来越多的证据表明化疗药物也会诱导EMT并增强所治疗癌细胞的恶性程度；然而，其机制仍不清楚。在此，我们研究了β-连环蛋白信号通路在阿霉素（Dox）诱导人胃癌细胞系BGC-823发生EMT中的作用。我们发现短暂给予Dox可诱导EMT并增强癌细胞的体外迁移能力。我们还发现Dox处理后β-连环蛋白信号通路被激活。用吲哚美辛（Indo）或小干扰RNA抑制β-连环蛋白可抑制Dox诱导的EMT并降低癌细胞迁移能力。我们的结果表明β-连环蛋白信号通路对Dox诱导的EMT至关重要。Indo和其他β-连环蛋白抑制剂可能在预防胃癌转移方面具有潜在意义。
