Study on the mechanism of chrysophanol inducing pyroptosis of gastric cancer cells by activating NLRP3 inflammasome

ObjectiveTo explore the effects of chrysophanol on pyroptosis of human gastric cancer cells and its possible mechanism.

MethodsThe human gastric cancer MKN28 cells were treated with chrysophanol at different concentrations(0, 5 and 10 μmol/L), NLRP3 inhibitor and caspase-1 inhibitor.The pyroptosis was detected using CCK-8 method, clone formation experiment and flow cytometry.The mRNA levels of pyroptosis and NLRP3 inflammasome-related proteins detected using real-time PCR.The protein expression levels of pyroptosis and NLRP3 inflammasome-related proteins were detected using Western blotting.

ResultsThe different concentrations of chrysophanol(0, 5 and 10 μmol/L) could decrease the cell viability and promote the occurrence of pyroptosison of MKN28 cells(P < 0.01).In a dose-dependent manner, the chrysophanol increased the mRNA and protein expression levels of NLRP3, caspase-1 and IL-1β in MKN28 cells(P < 0.01).The caspase-1 inhibitor VX-765 and NLPR3 inhibitor MCC950 were used to inhibit the expression of NLPR3 inflammasome, which could reduce the induced effect of chrysophanol on pyrotosis(P < 0.01).

ConclusionsThe chrysophanol can inhibit the proliferation, promote the release of LDH, increase the caspase-1 activity and induce the pyroptosis of gastric cancer MKN28 cells, and which might be related to the NLRP3/caspase-1 pathway.