title: Proton pump inhibitor pantoprazole inhibits the proliferation, self‑renewal and chemoresistance of gastric cancer stem cells via the EMT/β‑catenin pathways.
abstract: The cancer stem cell (CSC) model suggests that a small subset of cancer cells possess stem cell properties and plays a crucial role in tumor initiation, metastasis and resistance to anticancer therapy. Exploration of the specific therapies targeting at CSCs has been a crucial issue in antitumor research. Gastric cancer (GC) cells often exist in an ischemic microenvironment with acidic conditions in vivo, thus maintenance of cellular pH homeostasis is important for the survival and function of GC cells. Proton pump inhibitors (PPIs) may prevent intracellular proton extrusions which consequently reduce cancer cell survival under acidic conditions. The effects of PPIs on the suppression of the viability and invasiveness of GC cells have been reported, but the functional role of pantoprazole (PPZ) in GC cells remains unknown. In this study, we found that when cells were treated with PPZ, the 5‑fluorouracil (5‑FU) chemosensitivity was upregulated, meanwhile the sphere formation ability and the relative expression levels of stem cell markers CD44, CD24, ABCG2, EpCAM and Lgr5 were significantly decreased. It was hypothesized that PPZ inhibits the GC CSCs. Successively a sphere formation culture was performed to establish CSC models and the effect of PPZ on GC CSCs from SGC-7901 and HGC‑27 cells was explored. The addition of PPZ reduced the relative expression of CSC markers and anti‑drug markers accompanied by a decrease in proliferation, 5‑FU chemoresistance and self‑renewal capacity via epithelial‑mesenchymal transition (EMT)/β‑catenin pathways. The study suggests that PPZ could be a promising novel specific therapeutic strategy for targeting GC CSCs.
authors.affiliation: Department of Medical Oncology, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Shuitu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Medical Oncology, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Feng
authors.affiliation: Internal Medicine Department, Xiamen Navy Hospital, Xiamen, Fujian 361000, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Medical Records Room, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Zuhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Yubiao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Yingqin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Xiamen Haicang Hospital, Xiamen, Fujian 361026, P.R. China.
authors.forename: Yide
authors.initials: Y
authors.lastname: Chen
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000502:physiology; D013274:Stomach Neoplasms / Q000188:drug therapy; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D005472:Fluorouracil