Propofol Inhibits the Stem Characteristics and Tumor Growth of NSCLC by Altering the Expression and Localization of HDAC1

Most treatments for advanced NSCLC are no longer effective due to drug resistance, causing tumor progression. Cancer Stem Cells drive tumor development and treatment resistance. Moreover, HDAC1 and ARID1A play a role in tumor progression in EGFR-mutated NSCLC. This study aimed to investigate the role of HDAC1 in propofol-mediated antitumor effects in NSCLC using A549 and HCC827 cell lines and NSCLC nude mouse tumor models. Our results demonstrated that propofol effectively inhibited the stemness, activity, proliferation, migration, and invasion of NSCLC cells and tumor growth in NSCLC nude mice. Propofol also downregulated the levels of CD133, CD44, ABCG2, and ALDH1A1 in NSCLC cells. Moreover, propofol promoted the enrichment of HDAC1 and ARID1A in the ALDH1A1 promoter region by promoting EGFR degradation, leading to H3K27 deacetylation and subsequent transcriptional repression of ALDH1A1. Beyond altering the localization of HDAC1, propofol also inhibited the expression of HDAC1 and the level of miR-21-5p. MG132 eliminated the inhibition of propofol on HDAC1-mediated DGCR8 deacetylation. Furthermore, HDAC1 overexpression reversed the inhibitory effect of propofol on miR-21-5p expression and NSCLC tumor growth. Therefore, propofol inhibited HDAC1 expression to downregulate miR-21-5p, resulting in the inhibition of NSCLC tumors. As a conclusion, propofol inhibited the stem characteristics and growth of NSCLC tumor by regulating the translocation and expression of HDAC1. This study provides potential targets and treatment options for the treatment of advanced NSCLC tumors.

HDAC1; NSCLC; cancer stem genes; miR‐21‐5p; propofol.