文章：

DKK1通过激活PI3K/AKT通路促进胃癌上皮-间质转化及顺铂耐药

DKK1 Promotes Epithelial–Mesenchymal Transition and Cisplatin Resistance in Gastric Cancer via Activation of the PI3K/AKT Pathway

原文发布日期：27 September 2023

DOI: 10.3390/cancers15194756

类型: Article

开放获取: 是

英文摘要：

Chemotherapy is a classical method of cancer treatment. Cisplatin-based chemotherapy is a traditional and essential therapeutic approach in gastric cancer treatment. However, the development of drug resistance during treatment is a major obstacle that limits their further application, and molecular changes have occurred in the development of drug resistance. Here, we found that Dickkopf-related protein 1 (DKK1) is highly expressed in gastric cancer and related to poor prognosis in gastric cancer patients through public database mining. Next, we also identified that DKK1 is highly expressed in CDDP-resistant gastric cancer cell lines, supporting the notion that DKK1 is a necessary regulator of CDDP resistance. In terms of mechanistic research, our data reveal that DKK1 was able to activate the PI3K/AKT pathway and affect epithelial-to-mesenchymal transition, further contributing to CDDP resistance. Genetic knockdown and pharmacological inhibition of DKK1 recovered CDDP sensitivity both in vitro and in vivo. Therefore, our study highlights the potential of targeted inhibition of DKK1 to reverse CDDP resistance and alleviate metastatic properties in gastric cancer.

摘要翻译： 

化疗是癌症治疗的经典方法。基于顺铂的化疗是胃癌治疗中传统且重要的治疗手段。然而，治疗过程中产生的耐药性限制了其进一步应用，而耐药性的发展伴随着分子层面的变化。本研究通过公共数据库挖掘发现，Dickkopf相关蛋白1（DKK1）在胃癌中高表达，且与患者不良预后相关。进一步研究发现，DKK1在顺铂耐药的胃癌细胞系中表达显著升高，证实DKK1是顺铂耐药的关键调控因子。机制研究表明，DKK1能够激活PI3K/AKT信号通路并影响上皮-间质转化过程，从而促进顺铂耐药。通过基因敲低或药物抑制DKK1，可在体内外实验中恢复胃癌细胞对顺铂的敏感性。因此，本研究揭示了靶向抑制DKK1在逆转胃癌顺铂耐药及抑制转移特性方面的潜在价值。

原文链接：

DKK1 Promotes Epithelial–Mesenchymal Transition and Cisplatin Resistance in Gastric Cancer via Activation of the PI3K/AKT Pathway