Department of Anesthesiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Int J Oncol. 2017 Jul;51(1):307-315. doi: 10.3892/ijo.2017.3998. Epub 2017 May 16.
Gastric cancer is one of the common malignant diseases. The poor treatment outcome is mainly due to chemotherapeutic resistance. Therefore, it is important to determine the molecular mechanism of drug resistance in gastric cancer. To explore the mechanisms of cisplatin resistance in gastric cancer cells, several approaches were performed including MTT assay, real-time RT-PCR, western blot analysis, migration and invasion assays, wound healing assay, and transfection. We found that cisplatin-resistant (CR) gastric cancer cells acquired epithelial-mesenchymal transition (EMT) phenotype. The CR cells with EMT features obtained higher migratory and invasive activities. Moreover, we observed that TAZ was highly expressed in CR cells. Consistently, depletion of TAZ caused partial reversal of EMT to MET in CR cells. Our results suggest that TAZ plays a pivotal role in CR-induced EMT. Targeting TAZ could be a potential therapeutic strategy for gastric cancer.
胃癌是常见的恶性肿瘤之一。较差的治疗效果主要是由于化疗耐药。因此，确定胃癌中耐药的分子机制很重要。为了探讨胃癌细胞顺铂耐药的机制，我们进行了包括 MTT 检测、实时 RT-PCR、western blot 分析、迁移和侵袭检测、划痕愈合实验和转染在内的几种方法。我们发现，顺铂耐药（CR）胃癌细胞获得了上皮-间充质转化（EMT）表型。具有 EMT 特征的 CR 细胞获得了更高的迁移和侵袭活性。此外，我们观察到 TAZ 在 CR 细胞中高度表达。一致地，CR 细胞中 TAZ 的耗竭导致 EMT 向 MET 的部分逆转。我们的结果表明，TAZ 在 CR 诱导的 EMT 中起关键作用。靶向 TAZ 可能是治疗胃癌的一种潜在策略。
