Table 3.
Summary of experimental studies investigating the effects of proton pump inhibitors in gastric cancer cells
| Author, year | Study design | Type of PPI | Cell type | Main outcomes | Underlying hypothesis |
| Yeo et al[45], 2004 | In vitro, in vivo | Pantoprazole | MKN 45, MKN 28, AGS, SNU 601, RGM-1 (normal gastric mucosa cell) | Apoptotic cell death in gastric cancer cells, but not in normal gastric mucosal cells, induced by pantoprazole | Modulation of heat-shock proteins (HSP 70, HSP 27) |
| Chen et al[46], 2009 | In vitro | Pantoprazole | SGC7901 | Inhibition of V-H+-ATPase expression in a dose-dependent manner; enhancement of efficacy of anti-tumor drug (cisplatin) and increased apoptosis rate | Change of pH gradient (decrease of intracellular pH and reverse of the transmembrane pH gradient) |
| Shen et al[47], 2013 | In vitro | Pantoprazole | SGC7901 | Anti-proliferation, anti-invasive and pro-apoptotic effects, decrease of V-H+-ATPase expression | Inhibition of LRP6 in Wnt/β-catenin signaling |
| Chen et al[48], 2018 | In vitro, in vivo | Pantoprazole | SGC7901, SGC7901/MDR | Inhibition of V-H+-ATPase expression in, SGC7901/MDR cells | Inhibition of P-gp and MRP1, and downregulation of PI3K/Akt/mTOR/HIF-1α signaling pathway |
| Guan et al[49], 2017 | In vitro, in vivo | Esomeprazole | SGC7901 | Enhancement of efficacy of anti-tumor drugs (cisplatin, paclitaxel, 5-FU); Inhibition of transformation of CAF | Regulation of HIF-1α-FOXO1 axis and inhibition of release of exosome and exosome-related microRNAs (tumor invasion, metastasis and TGF-beta pathway) |
| Huang et al[73], 2013 | In vitro | Pantoprazole | SGC7901, GBC823, AGS | Inhibition of cellular proliferation and increase in the number of apoptotic cells | Inhibition of STAT3 |
| Koh et al[74], 2018 | In vitro, in vivo | Pantoprazole | AGS, MKN-28 | Inhibition of cellular invasion, migration and modulation of EMT markers | Induction of SHP-1 and inhibition of JAK2/STAT3 |
| Zhang et al[79], 2015 | In vitro | Pantoprazole | Adriamycin-resistant SGC7901 (SGC7901/ADR) | Inhibition of cellular migration/invasion and modulation of EMT markers in SGC7901/ADR cells | Inhibition of Akt/GSK-β/βcatenin signaling |
| Joo et al[80], 2018 | In vitro, in vivo | Pantoprazole | AGS | Enhanced cellular migration/invasion and anti-tumor effect of docetaxel by combination with minimal dose pantoprazole | Induction of SHP-1 and inhibition of JAK2/STAT3 |
PPI: Proton pump inhibitor; V-H+-ATPase: Vacuolar-H+-ATPase; LRP6: Low-density lipoprotein receptor related protein 6; MDR: Multidrug resistance; MRP1: Multidrug resistance-associated protein 1; mTOR: Mammalian target of rapamycin; HIF-1α: Hypoxia-inducible factor 1alpha; CAF: Cancer associated fibroblast; FOXO1: Forkhead box protein O1; TGF-beta: Tumor growth factor-beta; EMT: Epithelial-mesenchymal transition; STAT3: Signal transducer and activator of transcription 3; JAK2: Janus kinase 2; ADR: Adriamycin; GSK-β: Glycogen synthetase kinase-3-β.