Relationship of EGFR-TKI Targeted Therapy and Pyroptosis in Non-small Cell Lung Cancer

Abstract

Objective To explore the relationship between pyroptosis and treatment in non-small cell lung cancer patients treated with tyrosine kinase inhibitors targeted therapy. Methods Stable transfection strains with common EGFR mutations found in clinical practice were constructed through lentiviral transfection. LDH and Western blot experiments were conducted to determine the degree and mechanism of pyroptosis after osimertinib treatment. Animal experiments verified the effect of pyroptosis on treatment efficacy. ELISA was used to explore the potential connection between pyroptosis and tumor immunotherapy. Results After osimertinib treatment on stable lines, the EGFR-L858R mutation had obvious pyroptosis at the morphology and protein levels. Western blot experiment confirmed that pyroptosis was mediated by GSDME (P < 0.0001). Experiments through the overexpression of GSDME and corresponding animal studies discovered that the degree of pyroptosis affected the treatment outcome. Blood analysis revealed that the level of IL-1β secreted by EGFR-L858R and EGFR-L858R-GSDME-OE mice after treatment was higher than that of the control group (P < 0.0001), and it may regulate tumor immunity to a certain extent. Conclusion Osimertinib can induce pyroptosis in EGFR-L858R mutant strains mediated by GSDME, and the level of pyroptosis in cell lines is positively correlated with therapeutic effect to a certain extent.

Keywords

• non-small cell lung cancer
• pyroptosis
• tyrosine kinase inhibitors
• osimertinib