胰腺癌是目前最难治愈的人类癌症之一，仍然是一个关键的健康问题。胰腺癌最重要的特征之一是它能够在缺氧条件下生长。缺氧与癌细胞对放疗和化疗的抵抗力有关。它是胰腺癌遗传不稳定的主要原因，局部和全身耐药可能导致临床结果不佳。因此，鉴定低氧条件下发生的抗癌基因的基因表达变化可能会鉴定出新的治疗靶点。本研究的目的是探讨缺氧与化疗耐药之间的关系，并确定缺氧情况下癌症耐药相关基因表达的变化。胰腺癌细胞 (PANC-1) 每周暴露 3 次 8 小时缺氧（<1% 氧气），总共 20 次（慢性缺氧）或每周 2 次 72 小时缺氧，总共 10 次（慢性缺氧）。急性缺氧）。与常氧细胞相比，使用逆转录定量 PCR 阵列检查基因表达的变化。使用MTT细胞增殖测定评估缺氧细胞对阿霉素的化疗耐药性。慢性和急性缺氧都会诱导 PANC-1 胰腺癌细胞系对阿霉素产生化学耐药性。最大的变化发生在雌激素受体 Alpha 基因 (ESR1) 和 ETS Like-1 蛋白 (ELK1) 通路、核酸转录因子过氧化物酶体增殖物激活受体 (PPAR) 和细胞周期抑制剂细胞周期蛋白依赖性激酶抑制剂 1A (CDKN1A) 中。本研究表明，将细胞暴露于长期缺氧会导致不同的基因表达变化，涉及多效性途径，在诱导胰腺癌耐药性方面发挥作用。版权所有：© Zihlif 等人。

Pancreatic cancer is currently one of the least curable types of human cancer and remains a key health problem. One of the most important characteristics of pancreatic cancer is its ability to grow under hypoxic conditions. Hypoxia is associated with resistance of cancer cells to radiotherapy and chemotherapy. It is a major contributor to pancreatic cancer genetic instability, which local and systemic resistance that may result in poor clinical outcome. Accordingly, identifying gene expression changes in cancer resistance genes that occur under hypoxic conditions may identify a new therapeutic target. The aim of the present study was to explore the association between hypoxia and resistance to chemotherapy and determine the alteration in the expression of cancer resistance-related genes in the presence of hypoxia. Pancreatic cancer cells (PANC-1) were exposed to 8 h hypoxic episodes (<1% oxygen) three times/week for a total of 20 episodes (chronic hypoxia) or 72 h hypoxic episodes twice/week for a total of 10 episodes (acute hypoxia). The alterations in gene expression were examined using reverse transcription-quantitative PCR array compared with normoxic cells. Chemoresistance of hypoxic cells toward doxorubicin was assessed using MTT cell proliferation assay. Both chronic and acute hypoxia induced chemoresistance toward doxorubicin in PANC-1 pancreatic cancer cell line. The greatest changes occurred in estrogen Receptor Alpha Gene (ESR1) and ETS Like-1 protein (ELK1) pathways, in nucleic transcription factor Peroxisome proliferator-activated receptors (PPARs) and in a cell cycle inhibitor cyclin dependent kinase inhibitor 1A (CDKN1A). The present study demonstrated that exposing cells to prolonged hypoxia results in different gene expression changes involving pleotropic pathways that serve a role in inducing resistance in pancreatic cancer.Copyright: © Zihlif et al.