Separase Inhibition Enhances Gefitinib Sensitivity of Lung Cancer via PTBP1/TAK1/RIPK1-Mediated PANoptosis.

ABSTRACT: Gefitinib is the most frequently employed anti-lung cancer drug, but its clinical effectiveness is often compromised due to the development of drug resistance. Given that gefitinib failure to long-term inhibition of the growth of lung carcinoma cell lines, which mirrors the resistance observed in clinical patients, new approaches to improve the curative effect of gefitinib should be found. Surprisedly, inhibiting separase with the specific inhibitor Sepin-1 has been found to effectively enhance gefitinib-induced cytotoxic in lung cancer cell by promoting the development of PANoptosis, which includes pyroptosis, apoptosis, and necroptosis. Moreover, in vivo experiments also demonstrated that the combination of Sepin-1 and gefitinib can induce significant regression of lung xenograft tissues

SUBMITTER: Peng Z 

PROVIDER: S-EPMC12536889 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature