P4HB modulates epithelial‑mesenchymal transition and the β‑catenin/Snail pathway influencing chemoresistance in liver cancer cells

作者：Xing Ma, Jiening Wang, Juhua Zhuang, Xiaokun Ma, Ni Zheng, Yanan Song, Wei Xia · 发表于：Oncology Letters · 年份：2020 · DOI：10.3892/ol.2020.11569 · 被引用次数：43 · 研究领域：Epigenetics and DNA Methylation、Wnt/β-catenin signaling in development and cancer、Cancer-related gene regulation

The aim of the present study was to investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) in the chemoresistance of liver cancer. Drug‑resistant liver cancer cell lines, such as HepG2/adriamycin (ADR) cells, were treated and screened using adriamycin. Gene interference was used to silence the expression of P4HB in liver cancer cells. Cell viability, invasiveness and migration were assessed using CCK8, Transwell and wound healing assays, respectively. In addition, changes to key genes and proteins in the epithelial‑mesenchymal transition (EMT) and β‑catenin/Snail pathway were analyzed using reverse transcription‑quantitative PCR and western blotting. Drug‑resistant HepG2/ADR cells were successfully cultivated; the IC50 to ADR for HepG2/ADR and HepG2 cell lines was 4.85 and 0.61 µM, respectively. HepG2/ADR cells exhibited higher invasion and migration abilities compared with HepG2 cells (P<0.05). E‑cadherin mRNA and protein expression levels in HepG2/ADR cells were decreased significantly, whereas P4HB, N‑cadherin and vimentin mRNA and protein levels were significantly increased compared with HepG2 cells (all P<0.05). Knockdown of P4HB significantly decreased cell viability and the invasion and migration ability of HepG2/ADR cells. In addition, P4HB knockdown enhanced E‑cadherin mRNA and protein expression levels, whereas N‑cadherin, vimentin, total β‑catenin, nuclear β‑catenin and Snail mRNA and protein levels were significantly decreased (all P<0.05). Overall, ...