Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer
Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer
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DOI：
10.1016/j.molonc.2013.04.004
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发表时间：
2013-08-01
影响因子：
6.6
通讯作者：
Yamamoto, Kazuhide
中科院分区：
文献类型：
--
作者：
Horiguchi, Shigeru;Shiraha, Hidenori;Yamamoto, Kazuhide
背景和目标：Runt相关转录因子3（RUNX 3）是一种肿瘤抑制基因，在胃癌和其他癌症（包括胰腺癌）中表达。然而，RUNX 3在胰腺癌中的确切功能尚未完全阐明。在这项研究中，我们的目的是确定减少RUNX 3的表达在pancreaticcancer.Methods的效果：这项研究包括36例原发性胰腺癌，谁经历了pancreaticocompetration. The患者。采用免疫印迹法检测胰腺癌细胞系PANC-1、MIAPaCa-2、BxPC-3、SUIT-2和KLM-1中RUNX 3和多药耐药蛋白（MRP）的表达。通过cDNA转染细胞实现异位RUNX 3表达，并使用针对RUNX 3的小干扰RNA（siRNA）敲低内源性RUNX 3。使用MTT法评估吉西他滨存在下的细胞生长。结果：RUNX 3阳性和RUNX 3阴性胰腺癌患者的中位生存期分别为1006天和643天。外源性RUNX 3表达降低了内源性RUNX 3阴性细胞中MRP 1、MRP 2和MRP 5的表达，而RUNX 3 siRNA增加了内源性RUNX 3阳性细胞中这些基因的表达。外源性RUNX 3表达降低了RUNX 3阴性细胞中吉西他滨的IC 50。结论：RUNX 3表达的缺失通过诱导MRP表达而导致吉西他滨耐药，从而导致患者生存率低下。(C)2013年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Background & Aim: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene that is expressed in gastric and other cancers including pancreatic cancer. However, the precise function of RUNX3 in pancreatic cancer has not been fully elucidated. In this study, we aimed to determine the effect of decreased RUNX3 expression in pancreatic cancer.Methods: This study included 36 patients with primary pancreatic cancer, who had undergone pancreaticoduodenectomy. All patients were treated with 1000 mg/m2 gemcitabine after the surgery.The pancreatic cancer cell lines PANC-1, MIAPaCa-2, BxPC-3, SUIT-2, and KLM-1 were used for immunoblotting analysis of RUNX3 and multidrug resistance protein (MRP) expressions. Ectopic RUNX3 expression was achieved by cDNA transfection of the cells, and small interfering RNA (siRNA) against RUNX3 was used to knock down endogenous RUNX3. Cell growth in the presence of gemcitabine was assessed using the MTT assay.Results: Patients with RUNX3-positive and RUNX3-negative pancreatic cancer had a median survival of 1006 and 643 days, respectively. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5 in endogenous RUNX3-negative cells, whereas RUNX3 siRNA increased the expressions of these genes in endogenous RUNX3-positive cells. Exogenous RUNX3 expression decreased gemcitabine IC50 in RUNX3-negative cells.Conclusion: Loss of RUNX3 expression contributes to gemcitabine resistance by inducing MRP expression, thereby resulting in poor patient survival. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.