Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, PR China.
Pathobiology. 2017;84(1):38-48. doi: 10.1159/000447302. Epub 2016 Jul 27.
Pancreatic ductal adenocarcinoma (PDAC) exhibits poor prognosis and resistance to chemotherapy. This study was to identify the biomarkers associated with the progression, poor prognosis and chemoresistance of PDAC.
miR-34a and miR-150 levels in the plasma and tissues from PDAC patients were measured by real-time PCR. Xenograft PDAC tumor models were established in mice by inoculation of CD133+ stem cells isolated from PDAC tumors. Protein expression was measured by Western blot.
The plasma miR-34a and miR-150 levels were significantly lower in PDAC patients than in patients with benign pancreatic lesions and in healthy subjects. The miR-34a and miR-150 levels in the tumor tissues were significantly lower than in pancreatic tissues with benign lesions. The protein levels of CD133, Notch1, Notch2 and Notch4 receptors in PDAC tumor tissues were significantly higher than in pancreatic tissues with benign lesions. miR-34a injection significantly inhibited the tumor growth of PDAC tumors and sensitized the anticancer effects of 5-fluorouracil (5-FU). miR-34a significantly inhibited Notch1, Notch2 and Notch4 expression in xenograft tumor tissues in vivo and BxPC-3 cells in vitro. miR-34a and miR-150 significantly induced apoptosis and inhibited proliferation, invasion and migration in BxPC-3 cells. miR-34a, but not miR-150, significantly sensitized the anticancer effect of 5-FU in BxPC-3 cells in vitro.
A loss of expression of miR-34a, but not of miR-150, is associated with disease progression and poor prognosis in PDAC patients, and may be involved in the chemoresistance of PDAC cells.
胰腺导管腺癌（PDAC）表现出预后不良和对化疗的耐药性。本研究旨在鉴定与 PDAC 进展、不良预后和化疗耐药相关的生物标志物。
通过实时 PCR 测量 PDAC 患者血浆和组织中的 miR-34a 和 miR-150 水平。通过接种从 PDAC 肿瘤中分离的 CD133+干细胞，在小鼠中建立异种移植 PDAC 肿瘤模型。通过 Western blot 测量蛋白表达。
PDAC 患者的血浆 miR-34a 和 miR-150 水平明显低于良性胰腺病变患者和健康受试者。肿瘤组织中的 miR-34a 和 miR-150 水平明显低于良性病变的胰腺组织。PDAC 肿瘤组织中的 CD133、Notch1、Notch2 和 Notch4 受体蛋白水平明显高于良性病变的胰腺组织。miR-34a 注射显著抑制 PDAC 肿瘤的生长，并增强 5-氟尿嘧啶（5-FU）的抗癌作用。miR-34a 显著抑制体内异种移植肿瘤组织和体外 BxPC-3 细胞中的 Notch1、Notch2 和 Notch4 表达。miR-34a 和 miR-150 显著诱导 BxPC-3 细胞凋亡，抑制增殖、侵袭和迁移。miR-34a 而非 miR-150 显著增强 BxPC-3 细胞体外的 5-FU 抗癌作用。
miR-34a 的表达缺失，但不是 miR-150 的表达缺失，与 PDAC 患者的疾病进展和不良预后相关，并且可能参与 PDAC 细胞的化疗耐药性。
