Xu Jun, Zhang Shouru, Wang Rong, Wu Xingye, Zeng Li, Fu Zhongxue
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Gastrointestinal Surgery, Wuwei Tumor Hospital, Gansu 733000, China.
Biosci Rep. 2017 May 11;37(3). doi: 10.1042/BSR20160447. Print 2017 Jun 30.
Although, 5-Fluorouracil (5-FU) remains widely used in adjuvant therapy in patients with colon cancer, resistance to 5-FU-based chemotherapy is an important reason for treatment failure. Recent studies have reported that an enhanced reactive oxygen species (ROS) scavenging system shows drug resistance to 5-FU. Peroxiredoxin-2 (PRDX2), is an important member of the ROS scavenging system, and may be a potential target that promotes chemosensitivity to 5-FU in colon cancer. Here, we depleted PRDX2 by PRDX2-shRNA-LV transduction in two colon cancer cell lines and found that PRDX2 knockdown facilitates cell death, and apoptosis in 5-FU-treated colon cancer cells. In addition, we found that PRDX2 depletion in mice treated with 5-FU resulted in, inhibition of tumor growth, compared with mice treated with 5-FU alone. Our data also suggested that the PI3K/AKT signaling pathway links PRDX2 with 5-FU-induced apoptosis in colon cancer. Furthermore, when PRDX2 was overexpressed in colon cancer cells, we found increased p-AKT protein expression and reduced Bcl-2/Bax protein expression. PRDX2 and p-AKT protein expression were analyzed by immunohistochemistry technology in human colon carcinoma tissues. Pearson correlation coefficient is 0.873 and <0.05. PRDX2 depletion led to reduced p-AKT expression and PI3K/AKT pathway inhibition promoted cell apoptosis in HT29 cell line. Taken together, our study suggests that decreasing the expression of PRDX2 could be a promising strategy for increasing the sensitivity of colon cancer cells to 5-FU.
尽管5-氟尿嘧啶（5-FU）仍广泛用于结肠癌患者的辅助治疗，但对基于5-FU的化疗耐药是治疗失败的重要原因。最近的研究报道，增强的活性氧（ROS）清除系统显示出对5-FU的耐药性。过氧化物酶2（PRDX2）是ROS清除系统的重要成员，可能是促进结肠癌对5-FU化疗敏感性的潜在靶点。在此，我们通过PRDX2-shRNA-LV转导在两种结肠癌细胞系中敲低PRDX2，发现敲低PRDX2可促进5-FU处理的结肠癌细胞的细胞死亡和凋亡。此外，我们发现与单独用5-FU处理的小鼠相比，用5-FU处理的小鼠中PRDX2缺失导致肿瘤生长受到抑制。我们的数据还表明，PI3K/AKT信号通路将PRDX2与5-FU诱导的结肠癌凋亡联系起来。此外，当在结肠癌细胞中过表达PRDX2时，我们发现p-AKT蛋白表达增加，Bcl-2/Bax蛋白表达降低。通过免疫组织化学技术分析人结肠癌组织中PRDX2和p-AKT蛋白表达。Pearson相关系数为0.873，P<0.05。PRDX2缺失导致p-AKT表达降低，PI3K/AKT通路抑制促进HT29细胞系中的细胞凋亡。综上所述，我们的研究表明降低PRDX2的表达可能是提高结肠癌细胞对5-FU敏感性的一种有前景的策略。
