PPIs抑制空泡型质子泵逆转胃癌化疗多药耐药  

PPIs reverse multidrug resistance to chemotherapy in gastric cancer by inhibiting vacuolar H^+_-ATPase signal pathway

作　　者：李建琦[1] 陈敏[1] 邹晓平[1] 

机构地区：[1]南京大学医学院附属鼓楼医院消化科,江苏省南京市210008

出　　处：《世界华人消化杂志》2011年第31期3201-3206,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81071816;No.81101814;中央高校基本科研业务费基金资助项目;No.021414340018~~

摘　　要：肿瘤多药耐药性影响着胃癌化疗的效果,肿瘤微环境变化与多药耐药密切相关,而酸化与缺氧是微环境的两大特征.肿瘤细胞内无氧酵解生成大量H+,但却仍能维持胞内中性pH环境,推测与调节肿瘤泌酸功能的空泡型质子泵密切相关.胞外pH值的酸化可活化胞内PI3K/Akt信号通路,活化mTOR,上调HIF-1α,进而促进P-gp及MRP1的表达产生胃癌化疗耐药.PPIs可能是通过抑制空泡型质子泵的表达,改变肿瘤微环境,影响PI3K/Akt/mTOR/HIF-1α信号通路而逆转胃癌化疗多药耐药.Multidrug resistance（MDR） in gastric cancer influences the effects of chemotherapy.The change in tumor microenvironment is intimately asso-ciated with multidrug resistance.Acidification and hypoxia are the two major characteristics of tumor microenvironment.The glucose metabo-lism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acid-ity.But tumor cells can maintain intracellular to neutro-alkalinity.Vacuolar H＋-ATPases may be involved in this process by regulating H＋ ex-cretion.Acidif ication of extracellular pH would trigger the intracellular PI3K/Akt signal path-way,activate mTOR,up-regulate the expressionof HIF-1α,and promote the expression of P-gp and MRP1,resulting in multidrug resistance in gastric cancer.PPIs may change the tumor microenvironment by inhibiting the expression of vacuolar H＋-ATPases,trigger the PI3K/Akt/mTOR/HIF-1α signal pathway and reverse multi-drug resistance to chemotherapy in gastric cancer.

关 键 词：质子泵抑制剂 胃癌 多药耐药 

分 类 号：R735.2[医药卫生—肿瘤]