Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
Howard University School of Medicine, Washington DC 20059, USA.
Int J Oncol. 2019 Mar;54(3):991-1000. doi: 10.3892/ijo.2019.4676. Epub 2019 Jan 7.
Chemotherapy resistance (congenital or acquired) is one of the principal challenges for the treatment of pancreatic carcinoma. Recent evidence has demonstrated that epithelial to mesenchymal transition (EMT) is associated with chemoresistance in pancreatic carcinoma cells. However, the molecular mechanism underlying the development of chemoresistance remains unknown, and limited therapeutic options are available. Therefore, to anticipate individual chemosensitivity or acquired chemoresistance for patients with pancreatic carcinoma, predictive biomarkers are urgently required. Extensive evidence suggests that microRNAs (miRNAs) serve a crucial role in regulating EMT. The aim of this study was to examine the potential role of miRNA (miR)‑200b and miR‑301 in predicting the chemo‑responses to treatment for pancreatic carcinoma. The present results demonstrate that miR‑200b expression predicted chemo‑sensitivity and may have potential as a biomarker. In six different pancreatic carcinoma cell lines (Capan‑1, Capan‑2, Panc‑1, MIAPaCa‑2, BxPC‑3 and PL45 cells), the expression of miR‑200b correlated positively with chemosensitivity. Moreover, the enhanced expression of miR‑200b increased chemosensitivity and induced mesenchymal to epithelial transition. Conversely, miR‑301 modulated gemcitabine resistance and induced EMT through the downregulation of cadherin 1 expression. In addition, gemcitabine‑resistant cells (Capan‑2 and Panc‑1) exhibited upregulated miR‑301 expression and downregulated gemcitabine‑induced apoptosis. In summary, these two miRNAs may serve roles as biomarkers in pancreatic carcinoma, miR‑200b expression may predict chemosensitivity, and elevated miR‑301 expression may have potential applications in the prediction of acquired gemcitabine resistance.
化疗耐药（先天或获得性）是胰腺癌治疗的主要挑战之一。最近的证据表明上皮间质转化（EMT）与胰腺癌细胞的化疗耐药有关。然而，化疗耐药发展的分子机制尚不清楚，可用的治疗选择有限。因此，为了预测胰腺癌患者的个体化疗敏感性或获得性化疗耐药性，迫切需要预测生物标志物。大量证据表明 microRNAs（miRNAs）在调节 EMT 中起着至关重要的作用。本研究旨在探讨 miRNA（miR）-200b 和 miR-301 在预测胰腺癌治疗化疗反应中的潜在作用。本研究结果表明，miR-200b 的表达预测了化疗敏感性，可能具有作为生物标志物的潜力。在六种不同的胰腺癌细胞系（Capan-1、Capan-2、Panc-1、MIAPaCa-2、BxPC-3 和 PL45 细胞）中，miR-200b 的表达与化疗敏感性呈正相关。此外，miR-200b 的过表达增加了化疗敏感性并诱导了间质上皮转化。相反，miR-301 通过下调钙黏蛋白 1 的表达调节吉西他滨耐药并诱导 EMT。此外，吉西他滨耐药细胞（Capan-2 和 Panc-1）表现出上调的 miR-301 表达和下调的吉西他滨诱导的细胞凋亡。综上所述，这两种 miRNA 可能在胰腺癌中作为生物标志物发挥作用，miR-200b 的表达可预测化疗敏感性，上调的 miR-301 表达可能在预测获得性吉西他滨耐药性方面具有应用潜力。
