Objective: To explore the relationship between gasdermin D (GSDMD) and gastric cancer (GC) cell proliferation, and to determine whether the downregulated expression of GSDMD contributed to the tumorigenesis and proliferation of GC cells.
Methods: GSDMD expressions in GC tissues and matched adjacent non-cancerous tissues were assessed by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. The effect of GSDMD on cell proliferation in vitro was assessed by the colony formation assay and cell viability assays. In vivo, xenografted tumors in nude mice were evaluated. The cell cycle was analyzed by flow cytometry. In addition, the alterations of several cell cycle-related and cell signaling pathway proteins were analyzed by Western blot.
Results: GSDMD expression was decreased in GC, and the decreased expression of GSDMD could markedly promote the proliferation of tumors in vivo and in vitro. The downregulation of GSDMD accelerated S/G2 cell transition by activating extracellular signal regulated kinase, signal transducer and activator of transcription 3 and phosphatidylinositol 3 kinase/protein kinase B signaling pathways and regulating cell cycle-related proteins in GC.
Conclusion: GSDMD may protect against cell proliferation of GC, and it may be used as a diagnostic and treatment strategy for GC.
Keywords: cell cycle; cell proliferation; human GSDMD protein; mouse GSDMD protein; pyroptosis; stomach neoplasms.
© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.