MiR-200a-3p/ZEB1/IRF1-mediated PANoptosis prompts Xiangshaliujunzi decoction to overcome 5-fluorouracil resistance in gastric cancer

Figure 9 Regulation of ZEB1 to PANoptosis was mediated by IRF1 was present in the ZEB1 immunoprecipitation complex, and conversely, ZEB1 was detected in the IRF1 immunoprecipitation complex. Knocking down IRF1 expression in ZEB1 knockdown BGC-823/5-fluorouracil (5-FU) cells resulted in an increased expression of ZEB1. Knocking down ZEB1 expression also led to an increased expression of IRF1 ZEB1 knockdown in BGC-823/5-FU cells upregulated the expression of PANoptosis-related proteins. Simultaneous knockdown of both ZEB1 and IRF1 suppressed the expression of PANoptosis-related proteins. Levels of interferon (IFN)-γ, tumor necrosis factor (TNF-α), interleukin (IL)-1β, and IL-18 were increased in the culture medium of ZEB1 knockdown cells but decreased when both ZEB1 and IRF1 were knocked down. A: Immunoprecipitation complex of ZEB1 and IRF detected by co-immunoprecipitation; B: IRF1 expression in ZEB1 knock down and ZEB1/IRF1 knock down cells; C: ZEB1 expression in ZEB1 knock down and ZEB1/IRF1 knock down cells; D: PANoptosis-related proteins expression in ZEB1 knock down and ZEB1/IRF1 knock down cells; E: IFN-γ, TNF-α, IL-1β, and IL-18 secretory in culture medium of ZEB1 knock down and ZEB1/IRF1 knock down cells. ^aP < 0.05, ^bP < 0.01 vs sh-negative control (NC). ^dP < 0.05, ^eP < 0.01 vs sh-ZEB1 + sh-NC. XSLJZD: Xiangshaliujunzi decoction; NC: Negative control.