Fig. 5.

Pyroptosis in lung cancer. Increased GSDMD contributes to the proliferation of NSCLC cells. However, many potent anti-tumor drugs, such as polyphyllin VI and cucurbitacin B, induce NLRP3/caspase-1/GSDMD signaling pathway-mediated pyroptosis. Meanwhile, p53 induces pyroptosis to attenuate the proliferation of NSCLC cells by activating the NLRP3/ASC/caspase-1 signaling pathway. Additionally, chemotherapeutic drugs such as cisplatin and paclitaxel trigger caspase-3/GSDME-dependent pyroptosis to eliminate NSCLC cells and lead to the switch from apoptosis to pyroptosis in lung cancer cells. Notably, caspase-3/GSDME-dependent pyroptosis, which is mediated by cisplatin in normal tissues, contributes to the cisplatin-based side effects. Note: GSDMD, gasdermin D; NSCLC, non-small cell lung cancer; ASC, apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain; GSDME, gasdermin E