Abstract

In hepatocellular carcinoma (HCC), the presence of cancer stem cells (CSCs) have been linked to drug resistance, epithelial-mesenchymal transition (EMT), and cancer relapse. This study investigates the expression profile of ZEB1, ZEB2, ABCG2 in HCC-CSCs, and the role of EMT promoter ZEB2 in cells treated with resveratrol. The expression of ZEB1, ZEB2 and ABCG2 transcripts were analyzed in CD133⁺/CD44⁺ cells isolated from the PLC/PRF/5 cell line. ZEB2-dependent ABCG2 gene expression and the effects of resveratrol on proliferation, cell cycle and apoptosis were explored in SNU398 cell clones. An inverse correlation between ZEB1/ZEB2 and ABCG2 levels were observed both in CSCs and in ZEB2-knockdown cells. The resveratrol treatment significantly decreased cell viability, while promoting cell cycle arrest in ZEB2-independent manner. Interestingly, resveratrol-treated cells with low levels of ZEB2 were resistant to apoptosis. The interplay of expression levels of ABCG2 and ZEB family EMT transcription factors may play a role in establishing CSC-like phenotype in HCC cells resistant to resveratrol.

中文翻译：

---

伴随诱导ABCG2表达，ZEB2被下调的肝癌细胞对白藜芦醇具有抗性

摘要

在肝细胞癌（HCC）中，癌症干细胞（CSC）的存在与耐药性，上皮-间质转化（EMT）和癌症复发有关。这项研究调查ZEB1，ZEB2，ABCG2在肝癌CSCs中的表达谱，以及EMT启动子ZEB2在白藜芦醇处理的细胞中的作用。在从PLC / PRF / 5细胞系分离的CD133 ⁺ / CD44 ⁺细胞中分析了ZEB1，ZEB2和ABCG2转录物的表达。ZEB2 -依赖ABCG2研究了SNU398细胞克隆中的基因表达以及白藜芦醇对增殖，细胞周期和凋亡的影响。之间的逆相关ZEB1 / ZEB2和ABCG2无论在的CSC和ZEB2敲低细胞中观察到的水平。白藜芦醇处理显着降低细胞活力，同时以非依赖于ZEB2的方式促进细胞周期停滞。有趣的是，白藜芦醇处理过的ZEB2水平低的细胞对细胞凋亡具有抗性。ABCG2和ZEB家族EMT转录因子的表达水平之间的相互作用可能在建立抗白藜芦醇的HCC细胞中建立CSC样表型中发挥作用。