《生命科学》 2008, 20(5):

靶向肿瘤酸性微环境的抗肿瘤新策略

沈秋瑾，覃文新*

（上海交通大学肿瘤研究所癌基因及相关基因国家重点实验室，上海200032）

摘　要：摘　要：越来越多的体内体外实验及临床检测都证明了肿瘤酸性微环境对肿瘤的发生、发展和迁移起着重要作用。在肿瘤酸性微环境的重要调节因子中，V型ATP酶(V-ATPases)的作用至关重要。这些蛋白能将离子泵出膜外，在正常细胞和肿瘤细胞中都有着多种功能。本文回顾和总结了该领域的最新研究成果：在异种移植人肿瘤细胞的动物模型中，体内实验显示，采用小分子干扰RNA(siRNA)可抑制V-ATPases的功能，加入药物性质子泵抑制剂可显著地抑制人肿瘤细胞的生长。这些结果提示V-ATPases可作为癌症治疗中一个重要的新选择靶标。
关键词：V型ATP酶(V-ATPases)；肿瘤酸性微环境；质子泵抑制剂；细胞外基质；抗肿瘤药物
中图分类号：Q55; R979.1; R730.232　　文献标识码：A

Targeting tumor acidic microenvironment as a new strategy against cancer

SHEN Qiu-jin, QIN Wen-xin*

(Nantional Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China)

Abstract: Abstract: Growing evidence of experiment in vitro or in vivo and clinical detection suggests a key role of tumor acidic microenvironment in cancer development, progression, and metastasis. Among the key regulators of the tumor acidic microenvironment, vacuolar H+-ATPases (V-ATPases) play an important role. These proteins can pump ions across the membranes, and cover a number of functions in a variety of normal as well as tumor cells. We review and summerize some recent results showing that a molecular inhibition of V-ATPases by small interfering RNA (siRNA) in vivo as well as a pharmacologic inhibition through proton pump inhibitors (PPI) led to tumor cytotoxicity and marked inhibition of human tumor growth in xenograft models. These results propose V-ATPases as a key target for new strategies in cancer treatment.
Key words: vacuolar  H+-ATPases (V-ATPases); tumor acidic microenvironment; proton pump inhibitor (PPI); extracellular matrix (ECM); antineoplastic drugs