ArticleOncoTargets and therapy2018
Effects of proton pump inhibitors on reversing multidrug resistance via downregulating V-ATPases/PI3K/Akt/mTOR/HIF-1α signaling pathway through TSC1/2 complex and Rheb in human gastric adenocarcinoma cells in vitro and in vivo.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
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- Esomeprazole Potentiates the Cytotoxic Effects of Cisplatin in Gastric Carcinoma Cells.Journal of biochemical and molecular toxicology · 2025Article
- Prophylactic proton pump inhibitor usage and new-onset acute kidney injury in critically ill patients: a retrospective analysis.Clinical kidney journal · 2025Article
- LINC01224 promotes the Warburg effect in gastric cancer by activating the miR-486-5p/PI3K axis.In vitro cellular & developmental biology. Animal · 2025Article
- V-ATPase in cancer: mechanistic insights and therapeutic potentials.Cell communication and signaling : CCS · 2024Review
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
- Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration.Biology open · 2024Review
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.International journal of molecular sciences · 2024Review
- Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease.Frontiers in pharmacology · 2024Article
- Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters.Nature reviews. Cancer · 2023Review
- Role of N6-methyladenosine RNA modification in gastric cancer.Cell death discovery · 2023Review
- Intracellular Acidification in a Rat C6 Glioma Model following Cariporide Injection Investigated by CEST-MRI.Metabolites · 2023Article
- Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.PLoS pathogens · 2023Article
- Esomeprazole Alleviates Cisplatin Resistance by Inhibiting the AKT/mTOR Pathway in Ovarian Cancer Cells.OncoTargets and therapy · 2023Article
- Effect of Esomeprazole Treatment on Extracellular Tumor pH in a Preclinical Model of Prostate Cancer by MRI-CEST Tumor pH Imaging.Metabolites · 2022Article
- In Vivo MRI-CEST Tumor pH Imaging Detects Resistance to Proton Pump Inhibitors in Human Prostate Cancer Murine Models.Cancers · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur study aimed to explore the effects of PPIs on reversing multidrug resistance (MDR) to chemotherapy in gastric cancer by inhibiting the expression of V-ATPases and the PI3K/Akt/mTOR/HIF-1α signal pathway.
methodsThe gastric cancer cell lines SGC7901 and the multidrug resistance cell lines SGC7901/MDR were pretreated by the pantoprazole or the esomeprazole, respectively. Real-time PCR was used to determine mRNA levels, and western blotting and immunofluorescent staining analyses were employed to determine the protein expressions and intracellular distributions of the V-ATPases, PI3K, Akt, mTOR, HIF-1α, P-gp and MRP1 before and after PPIs pretreatment. SGC7901/MDR cells were planted on the athymic nude mice. Then the effects of PPZ pretreatment and/or ADR were compared by determining the tumor size, tumor weight and nude mice weight.
resultsPPIs pretreatment could inhibit mRNA levels of V-ATPases, MDR1 and MRP1, PI3K, Akt, mTOR and HIF-1α. PPIs inhibited V-ATPases and down-regulated the expressions of P-gp and MRP1. And further to block the expression of mTOR by Rapamycin could obviously inhibit the expressions of HIF-1α, P-gp and MRP1 in a dose-dependent manner. Therefore, PPIs inhibited the expressions of V-ATPases and then reversed MDR of the chemotherapy in gastric cancer by inhibiting P-gp and MRP1, and it could be speculated that the mechanism might be closely related to down-regulating the PI3K/Akt/mTOR/HIF-1α signaling pathway. Meanwhile, PPIs also could inhibit the expressions of TSC1/TSC2 complex and Rheb which might be involved into regulating the signaling pathway intermediately. The weight growth rate of the mice bearing tumor in the treatment group was lower than that of the nude mice in the normal group, while the weight growth rate of the mice in control group was significantly lower than that of the normal group and the treatment group, presenting a downward trend.
conclusionTherefore, PPIs inhibited the expressions of V-ATPases and then reversed MDR of the chemotherapy in gastric cancer by inhibiting P-gp and MRP1, and it could be speculated that the mechanism might be closely related to down-regulating the PI3K/Akt/mTOR/HIF-1α signaling pathway, and also to inhibiting the expressions of TSC1/TSC2 complex and Rheb which might be involved into regulating the signaling pathway intermediately.
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