临床肿瘤学杂志

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自噬在低氧诱导的抗肿瘤耐药中的研究进展

张雯综述,崔越宏,刘天舒审校
  

  1. 200052 上海 复旦大学附属中山医院肿瘤内科
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2013-11-30 发布日期:2013-11-30

Research progress of cell autophagy in hypoxiainduced antitumor drug resistance

ZHANG Wen,CUI Yuehong, LIU Tianshu   

  1. Department of Medical Oncology, the Affiliated Zhongshan Hospital, Fudan University, Shanghai 200052, China
  • Received:1900-01-01 Revised:1900-01-01 Online:2013-11-30 Published:2013-11-30

摘要: 自噬是普遍存在于大部分真核细胞中的一种保守的分解代谢过程,是溶酶体对自身结构的吞噬和降解。它不仅是细胞内的再循环系统,也是程序性死亡的形式之一。在人类多种肿瘤中存在自噬活性的改变,而自噬对肿瘤发生发展的作用也莫衷一是。实体肿瘤生长迅速,局部常处于缺血、缺氧的微环境中,而缺氧是产生肿瘤耐药的重要因素之一。越来越多的研究发现自噬参与了低氧诱导肿瘤耐药过程,低氧可通过缺氧诱导因子1、磷酸腺苷激活的蛋白激酶和激活转录因子4等多条途径诱导自噬,最终导致肿瘤耐药。因此,自噬极有可能是对抗肿瘤耐药的潜在靶点,抑制自噬有望成为有效的肿瘤治疗策略。

Abstract: Autophagy is a conserved catabolism process existing in most eukaryotes with the phagocytosis and degradation of its own structure by lysosomal. It is not only an intracellular recycling system but also one form of programed cell death. The change of autophagic activity has been detected in varieties of tumors, while the roles of autophagy are paradoxical in the growth and development of tumors. With the rapid growth of solid tumors, the tumor microenvironment is characterized by ischemia and hypoxia, which is an important factor in promoting drug resistance. More and more studies have demonstrated that autophagy also plays a key role in the process of hypoxiainduced drug resistance. Hypoxia can induce autophagy through at least three pathways including hypoxiainducible factor 1, AMPactivated protein kinase and activating transcription factor 4. Therefore, autophagy is a potential target for antitumor drug resistance, and inhibiting autophagy is expected to be an effective strategy in the treatment of cancer.

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