靶向肿瘤酸性微环境的抗肿瘤新策略-生命科学.PDF

20 5 Vol. 20, No. 5 2008 10 Chinese Bulletin of Life Sciences Oct., 2008 1004-0374(2008)05-0795-05 200032 V ATP (V-ATPases) RNA(siRNA) V-ATPases V- ATPases V ATP (V-ATPa ses) Q55; R979.1; R730.232A 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: 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 [5] pH [1]