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GSDME mediates caspase-3-dependent pyroptosis in gastric cancer

  • Yubin Wang
  • , Bo Yin
  • , Dinuo Li
  • , Guijun Wang
  • , Xiangdong Han
  • , Xuejun Sun

Research output: Contribution to journalArticlepeer-review

287 Scopus citations

Abstract

Gastric cancer is a malignancy that starts from the cells in the stomach with relatively low overall survival rate. Chemotherapy following resection surgery has been recommended as a curative strategy for gastric cancer. However, the mechanism of the chemotherapy drugs on gastric cancer is not completely understood. Pyroptosis is a form of programmed cell death and plays critical role in immunity. The role of pyroptosis on cancer cells is less known. In this study, we treated SGC-7901 and MKN-45 with 5-FU and found that the cell viability was significantly decreased. The release of LDH and the percentage of PI and APC Annexin-V double positive cells after 5-FU treatment were elevated compared to control group. Moreover, there were large bubbles blowing from the membrane of 5-FU-treated cells and the cleavage of GSDME but not GSDMD, which were blocked by the silence or specific inhibitor of caspase-3. Additionally, GSDME knockout by CRISPR-Cas9 switched 5-FU induced pyroptosis into apoptosis in SGC-7901. In conclusion, our findings firstly revealed that GSDME switches chemotherapy drug-induced caspase-3 dependent apoptosis into pyroptosis in gastric cancer cells.

Original languageEnglish
Pages (from-to)1418-1425
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume495
Issue number1
DOIs
StatePublished - 1 Jan 2018
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Caspase-3
  • GSDME
  • Gastric cancer
  • Pyroptosis

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