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. 2018 Jan 1;495(1):1418-1425.
doi: 10.1016/j.bbrc.2017.11.156. Epub 2017 Nov 26.

GSDME Mediates caspase-3-dependent Pyroptosis in Gastric Cancer

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GSDME Mediates caspase-3-dependent Pyroptosis in Gastric Cancer

Yubin Wang et al. Biochem Biophys Res Commun. .

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.

Keywords: Caspase-3; GSDME; Gastric cancer; Pyroptosis.

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