Decrease of AIM2 mediated by luteolin contributes to non-small cell lung cancer treatment.

ABSTRACT: Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. Although extensive studies showed that luteolin exhibited antitumor effects against NSCLC, the mechanism has not been fully established. In the present study, we found that luteolin significantly reduced the expression of absent in melanoma 2 (AIM2) at both mRNA and protein levels leading to the suppression of AIM2 inflammasome activation, which induced G2/M phase arrest and inhibited epithelial-mesenchymal transition (EMT) in NSCLC. Furthermore, the inhibitory effects of luteolin on NSCLC cells were abolished by the knockdown of AIM2. On the contrary, the antitumor effects of luteolin could be notably reversed by the overexpression of AIM2. In addition, luteolin reduced poly(dA:dT)-induced caspase-1 activation and IL-1? cleavage in NSCLC cells. These findings suggested that AIM2 was essential to luteolin-mediated antitumor effects. The antitumor effects of luteolin, which were closely associated with AIM2, were also confirmed in the A549 and H460 xenograft mouse models. Collectively, our study displayed that the antitumor effects of luteolin on NSCLC were AIM2 dependent and the downregulation of AIM2 might be an effective way for NSCLC treatment.

SUBMITTER: Yu Q 

PROVIDER: S-EPMC6399355 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature