|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (2009) 33, 10081019 (Printed in Great Britain)
Effects and mechanisms of proton pump inhibitors as a novel chemosensitizer on human gastric adenocarcinoma (SGC7901) cells
Min Chena1, Xiaoping Zoub*1, Hesheng Luoa**, Jun Caob, Xiaoqi Zhangb, Bin Zhangb and Wenjia Liub
aDepartment of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China
bDepartment of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing 210008, PR China
Upregulation of proton extrusion is critical for tumor cell survival in an ischemic microenvironment with a lower extracellular pH (pHe). Lower pHe and higher intracellular pH (pHi) benefit cancer cells for invasion and growth. Vacuolar H+-ATPases (V-H+-ATPases) play a critical role in regulating the transmembrane pH gradient. Proton Pump Inhibitors (PPI), mainly treating acid-related diseases, could inhibit the expression of V-H+-ATPases. We have investigated whether PPI decreases the pHi of the human gastric adenocarcinoma cell line, SGC7901, by inhibiting V-H+-ATPases so as to enhance the cytotoxicity of anti-tumor drugs. We have assessed the optimal treatment time, pretreatment dosage of PPI and the possible mechanism of action. PPI exceeding 10
Key words: Vacuolar H+-ATPases, Tumor acidity, Proton pump inhibitors, Transmembrane pH gradient.
1Min Chen and Xiaoping Zou contributed equally to this work.
*Corresponding author. Tel.: +86 25 88304616 20601; fax: +86 25 83105206.
**Corresponding author. Tel.: +86 13618644197; fax: +86 27 88042292.
Received 28 December 2008/9 April 2009; accepted 7 May 2009doi:10.1016/j.cellbi.2009.05.004