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活性氧介导的肿瘤微环境在胰腺癌发生与发展中作用的研究进展

陶旭锋¹, Vay Liang W(Bill) Go², 肖桂山^1,2,3,*

¹大连理工大学化工学院，大连 116024；²美国加州大学洛杉矶分校大卫格芬医学院胰腺疾病中心，加利福尼亚州，洛杉矶；³美国克里顿大学医学中心骨质疏松研究中心功能基因组学和蛋白质组学实验室，内布拉斯加州，奥马哈

摘要

胰腺癌是一种在全世界范围内发病率和死亡率都很高的恶性肿瘤，当前缺少有效的手术方法和治疗药物。近年来，活性氧(reactive oxygen species, ROSs)已成为胰腺癌研究领域的热点。ROSs可调节肿瘤微环境(tumor microenvironment, TME)、肿瘤干细胞(cancer stem cells, CSCs)更新和上皮-间质转化(epithelial-mesenchymal transition, EMT)等过程，从而导致胰腺癌的耐药和复发。当前，包括免疫浸润、成纤维细胞、血管和细胞外基质在内的TME已成为肿瘤研究的热点。同时，已有大量文献报道ROSs介导的TME在胰腺癌的发生与发展中具有重要的作用，靶向调节ROSs可能是治疗胰腺癌的一种方法。因此，本文综述了ROSs在胰腺癌肿瘤发生和耐药中的调控作用、ROSs在胰腺癌信号转导中的作用以及ROSs在胰腺癌基质细胞中的作用，并总结了靶向调节ROSs的抗胰腺癌的潜在药物。

关键词： 胰腺癌; 肿瘤微环境; 活性氧; 肿瘤干细胞; 耐药

分类号：R735.9

Progress on the role of reactive oxygen species-mediated tumor microenvironment in pancreatic cancer

Xufeng Tao¹, Vay Liang W(Bill) Go², Gary Guishan Xiao^1,2,3,*

¹School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China；²The UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States；³Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, United States

Abstract

Pancreatic cancer (PC) is a devastating malignant tumor with high incidence and mortality rate worldwide. Meanwhile, the surgical approaches and drugs of this disease remain challenging. In recent years, reactive oxygen species (ROSs) study has become a hotspot in the field of PC research. ROSs may regulate tumor microenvironment (TME), cancer stem cells (CSCs) renewal and epithelial-mesenchymal transition (EMT), which result in drug-resistance and recurrence of the PC. Currently, TME that includes 

immune infiltrates, fibroblasts, vascular vessels and extracellular matrix has become a hotspot in the cancer research. Meanwhile, numerous researches have shown that ROSs-mediated TME plays a central role in the occurrence and development of PC. Targeting ROSs may be promising therapeutic treatments for the PC patients. Therefore, the purposes of the review were manifold: (1) to summarize the regulations of ROSs in tumorigenesis and drug-resistance of PC; (2) to investigate the modulation of ROSs in signaling cascades in PC; (3) to study the effects of ROSs in stromal cells in PC; (4) to generalize the potent therapies targeting ROSs in PC. Overall, this review summarized the current status of ROSs in PC research and suggested some potential anti-PC drugs that may target ROSs.

Key words: pancreatic cancer; tumor microenvironment; reactive oxygen species; cancer stem cells; drug-resistance

收稿日期：2020-05-27　　录用日期：2020-12-10

通讯作者：肖桂山　　E-mail: gxiao@dlut.edu.cn

DOI: 10.13294/j.aps.2021.0011

引用本文：

陶旭锋, Vay Liang W(Bill) Go, 肖桂山. 活性氧介导的肿瘤微环境在胰腺癌发生与发展中作用的研究进展[J]. 生理学报 2021; 73 (2): 197-207.

Xufeng Tao, Vay Liang W(Bill) Go, Gary Guishan Xiao. Progress on the role of reactive oxygen species-mediated tumor microenvironment in pancreatic cancer. Acta Physiol Sin 2021; 73 (2): 197-207