Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, PR China.
Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, PR China.
Biochem Biophys Res Commun. 2014 Jun 13;448(4):424-9. doi: 10.1016/j.bbrc.2014.04.127. Epub 2014 May 4.
The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-l-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.
肿瘤中糖酵解和质子分泌的增加被认为有助于肿瘤发生和转移过程中癌细胞的增殖和侵袭。在这里，用质子泵抑制剂（PPI）兰索拉唑（LPZ）处理人乳腺癌细胞以剂量依赖性方式诱导细胞凋亡。在裸鼠 MDA-MB-231 异种移植的植入中，LPZ 的给药显著抑制肿瘤发生并诱导肿瘤细胞的大规模凋亡。LPZ 显著抑制细胞内质子外排，诱导细胞内 ATP 水平增加、溶酶体碱化和活性氧（ROS）在乳腺癌细胞中的积累。ROS 清除剂 N-乙酰-L-半胱氨酸（NAC）和二苯基碘（DPI），一种 NADPH 氧化酶（NOX）的特异性药理学抑制剂，显著消除 LPZ 诱导的乳腺癌细胞中 ROS 的积累。我们的结果表明，LPZ 可作为治疗乳腺癌的新药物。
