Proton pump inhibitors increase the chemosensitivity of patients with advanced colorectal cancer.

Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice. Importantly, a retrospective clinical study of CRC patients receiving the FOLFOX or CapeOx regimen indicates that PPIs increase the chemosensitivity of CRC patients. Patients who received the FOLFOX regimen with a PPI had better overall survival (OS) and progression-free survival (PFS) than patients who did not receive a PPI during FOLFOX chemotherapy. The incidence of nausea and vomiting was also lower in patients receiving a PPI with FOLFOX or CapeOx than in those who did not receive PPI. These results indicate that PPIs may be successfully incorporated into the FOLFOX regimen to increase the chemotherapeutic effect for CRC patients.