Proton pump inhibitor: The dual role in gastric cancer

World J Gastroenterol. 2019 May 7;25(17):2058-2070. doi: 10.3748/wjg.v25.i17.2058.


Proton pump inhibitors (PPIs) are one of the most frequently used medications for upper gastrointestinal diseases. However, a number of physicians have raised concern about the serious side effects of long-term use of PPIs, including the development of gastric cancer. Recent epidemiological studies have reported a significant association between long-term PPI intake and the risk of gastric cancer, even after successful Helicobacter pylori eradication. However, the effects of PPIs on the development of pre-malignant conditions such as atrophic gastritis or intestinal metaplasia are not fully known, suggesting the need for comprehensive and confirmative studies are needed in the future. Meanwhile, several experimental studies have demonstrated the effects of PPIs in reducing chemoresistance in gastric cancer cells by modulating the acidic microenvironment, cancer stemness and signal transducer and activator of transcription 3 (STAT3) signaling pathway. The inhibitory effects of PPIs on STAT3 activity may overcome drug resistance and enhance the efficacy of conventional or targeted chemotherapeutic agents. Taken together, PPIs may "play dual role" in gastric carcinogenesis and treatment of gastric cancer.

Keywords: Drug resistance; Gastric cancer; Proton pump inhibitor; Signal transducer and activator of transcription 3.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Resistance, Neoplasm*
  • Gastritis, Atrophic / diagnosis
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Intestines / pathology*
  • Proton Pump Inhibitors / therapeutic use*
  • Risk Factors
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Stomach Neoplasms / drug therapy*
  • Treatment Outcome
  • Tumor Microenvironment


  • Proton Pump Inhibitors
  • STAT3 Transcription Factor
  • STAT3 protein, human