18 β-Glycyrrhetinic Acid Inhibits Malignant Progression of Prostate Cancer via Regulation of Autophagy and EMT...

Prostate cancer (PCa) is one of the most common malignancies in men, and its progression is closely related to epithelial-mesenchymal transition (EMT) and autophagy imbalance. 18β-Glycyrrhetinic acid (18β-GA) has been reported to exhibit various anti-tumour activities. This study aims to systematically evaluate the impact of 18β-GA on the malignant biological behaviours of PCa and explore its potential molecular mechanisms.

The human PCa cell lines LNCaP and PC-3 were used to evaluate the inhibitory effects of 18β-GA on malignant progression. The potential mechanisms were further explored by assessing EMT markers, autophagy-related proteins and angiogenesis. The role of the PTEN/PI3K/mTOR pathway in 18β-GA's effects was explored through siRNA-mediated PTEN knockdown and Western blot analysis. A PCa xenograft model was established in vivo to assess the impact of 18β-GA on tumour growth.

18β-GA significantly inhibited the viability, proliferation, migration and invasion of LNCaP and PC-3 cells, while promoting apoptosis, with no significant toxicity to RWPE-1 cells. 18β-GA upregulated E-cadherin and Claudin-1, while downregulating N-cadherin, Vimentin, Snail and MMP2/9, thus inhibiting the EMT process and reducing the angiogenesis capacity and VEGF expression in HUVECs. Additionally, 18β-GA increased the LC3-II/LC3-I ratio, upregulated Beclin1 and ATG7 and downregulated p62, indicating activation of autophagic flux. Mechanistic studies revealed that 18β-GA upregulated PTEN expression and inhibited PI3K and mTOR phosphorylation. PTEN knockdown partially reversed its effects on autophagy, EMT and malignant phenotypes. In vivo experiments further confirmed that 18β-GA significantly suppressed xenograft tumour growth and exhibited anti-tumour effects.

18β-GA inhibits the malignant progression of PCa cells and xenograft tumour growth by upregulating PTEN and inhibiting the PI3K/mTOR axis, synergistically activating autophagy and inhibiting EMT and angiogenesis. 18β-GA holds promise as a potential anti-PCa drug targeting the PTEN/PI3K/mTOR pathway, jointly regulating autophagy and EMT.