β-Elemene inhibits epithelial-mesenchymal transformation in non-small cell lung cancer by targeting ALDH3B2/RPSA axis.

The pharmacological mechanism of β-elemene in non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we identified aldehyde dehydrogenase 3B2 (ALDH3B2) as a pivotal target for β-elemene's anti-tumor effects in NSCLC by bioinformatic analysis. The overexpression of ALDH3B2 is specifically associated with the malignancy of NSCLC and the poor prognosis in patients with lung adenocarcinoma. Furthermore, we observed a positive correlation between ALDH3B2 levels and the sensitivity of cells to β-elemene. Additionally, we confirmed that β-elemene suppresses ALDH3B2 expression in PC-9 and NCI-H1373 cell lines. Notably, ALDH3B2 overexpression in NCI-H1373 cells resulted in enhanced migration, invasion, and a prominent epithelial-mesenchymal transition (EMT), which could be attenuated by β-elemene via inhibition of ALDH3B2 expression. Subsequent investigations demonstrated that ALDH3B2 overexpression upregulated ribosomal protein SA (RPSA) expression. β-elemene counteracted the upregulation of RPSA by suppressing ALDH3B2. Furthermore, knocking down of ALDH3B2 and β-elemene treatment significantly reduced the activation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways via suppression of RPSA. In summary, our research uncovers that in NSCLC, ALDH3B2 functions as an oncogenic protein, promoting tumor progression. Meanwhile, β-elemene inhibits EMT of NSCLC by inhibition of ALDH3B2/RPSA axis and subsequently downregulating AKT and ERK signaling pathways. Our study highlights the significant role of ALDH3B2 in the progression of NSCLC, signifying it as a potential pharmacodynamic biomarker for β-elemene. These findings enrich the understanding of anti-tumor pharmacological mechanism of β-elemene, and provides new theoretical and experimental foundations for its potential application in the treatment of NSCLC.