Studies on the inhibitory effect and mechanism of ETP compound GQQ-ZML-2 from marine products on the proliferation of H358 cells
Objective To investigate the proliferation inhibitory effect of compound GQQ-ZML-2 on the H358 cells(KRASG12C)and its mechanism.Methods The cytotoxicity of GQQ-ZML-2 to different cancer cells was determined by SRB method(SRB method).The cell cycle and apoptosis were detected by flow cytometry.Intracellular total reactive oxygen species(ROS)were detected by fluorescence probe DCFH-DA.The expression levels of related signaling proteins were detected by Western blotting.Results GQQ-ZML-2 selectively inhibited the proliferation of H358 cells,inhibited clonal formation in a concentration-dependent manner,and induced cell apoptosis by blocking the cell cycle in G2/M phase.Mechanism studies have shown that GQQ-ZML-2 induces KRASG12C-dependent ROS production and inhibits AKT/mTOR and JAK2/STAT3 signaling pathways.Conclusion GQQ-ZML-2 is a novel marine compound that selectively inhibits the proliferation of H358 cells,and its mechanism relates to the induction of ROS increase dependent on KRASG12C.This study provides experimental basis to develop novel antagonistic agent for cancer with KRASG12Cmutant.
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