Department of Breast Disease Diagnosis, Treatment Centre, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Department of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong 266021, P.R. China.
Mol Med Rep. 2020 Oct;22(4):3183-3190. doi: 10.3892/mmr.2020.11414. Epub 2020 Aug 4.
Multidrug resistance (MDR) is a major cause of disease relapse and mortality in breast cancer. Paired‑related homeobox 1 (PRRX1) is associated with the epithelial‑mesenchymal transition (EMT), which is involved in tumor development, including cell invasion and MDR. However, the effect of PRRX1 on MDR had not clearly established. The present study investigated the influence of PRRX1 on MDR and the underlying molecular mechanisms in MCF‑7 breast cancer cells. MCF‑7 cells were divided into PRRX1+ group (cells transfected with a recombinant plasmid carrying the PRRX1 gene), negative control group (cells transfected with a blank vector) and blank group (untreated cells). It was found that the relative protein and mRNA expression levels of PRRX1, N‑cadherin, vimentin and P‑glycoprotein were significantly higher in PRRX1‑overexpressing MCF‑7 cells compared with those in control cells. The half‑maximal inhibitory concentration of three groups after treatment with docetaxel and cis‑platinum complexes were significantly higher in PRRX1‑overexpressing MCF‑7 cells compared with those in control cells. Furthermore, relative PTEN expression decreased significantly and levels of phosphorylated PI3K and AKT increased substantially in PRRX1‑overexpressing MCF‑7 cells. These results indicated that PRRX1 overexpression may induce MDR via PTEN/PI3K/AKT signaling in breast cancer. It is highly recommended that PRRX1 gene expression detection should be performed in patients with breast cancer to aid the selection of more appropriate treatments, which will lead to an improved prognosis in clinical practice.
多药耐药（MDR）是乳腺癌疾病复发和死亡的主要原因。配对相关同源盒 1（PRRX1）与上皮-间充质转化（EMT）有关，EMT 参与肿瘤的发展，包括细胞侵袭和 MDR。然而，PRRX1 对 MDR 的影响尚未明确。本研究探讨了 PRRX1 对 MCF-7 乳腺癌细胞 MDR 的影响及其潜在的分子机制。将 MCF-7 细胞分为 PRRX1+组（转染携带 PRRX1 基因的重组质粒的细胞）、阴性对照组（转染空载体的细胞）和空白组（未处理的细胞）。结果发现，与对照组细胞相比，过表达 PRRX1 的 MCF-7 细胞中 PRRX1、N-钙黏蛋白、波形蛋白和 P-糖蛋白的相对蛋白和 mRNA 表达水平显著升高。用多西紫杉醇和顺铂复合物处理后，PRRX1 过表达 MCF-7 细胞的半数最大抑制浓度明显高于对照组细胞。此外，PRRX1 过表达 MCF-7 细胞中相对 PTEN 表达明显下降，磷酸化 PI3K 和 AKT 水平显著升高。这些结果表明，PRRX1 过表达可能通过 PTEN/PI3K/AKT 信号通路诱导乳腺癌的 MDR。强烈建议对乳腺癌患者进行 PRRX1 基因表达检测，以帮助选择更合适的治疗方法，从而改善临床实践中的预后。
