Mechanism of astragaloside IV enhancing the sensitivity of non-small cell lung cancer to bevacizumab via the lncRNA-PVT1/miR-361-3p/HMGB1 axis.

OBJECTIVE

This study investigated how astragaloside IV (AST-IV) enhances the responsiveness of non-small cell lung cancer (NSCLC) to bevacizumab (BV) via the lncRNA-PVT1/miR-361-3p/HMBG1 axis.

METHODS

Human NSCLC A549 cells were cultured in vitro. oe-NC, A549 cells were transfected with oe-PVT1, oe-HMGB1, mimics NC, and mimics miR for 24 h using transfection reagents and then treated with 50 ng/mL AST-IV and 25 μmol/L BV for 24 h. Expression levels of PVT1, miR-361-3p, and HMGB1 were quantified by RT-qPCR, while protein levels of HMGB1, Ki67, Bax, and Cleaved-caspase-3 were examined through western blot analysis. Proliferation was measured using the CCK-8 assay, and apoptosis was assessed via flow cytometry. The targeting interactions between PVT1 and miR-361-3p, as well as miR-361-3p and HMGB1 were predicted by the BiBiServ2 database and verified by the luciferase reporter assay.

RESULTS

AST-IV and BV-treated A549 cells exhibited significantly inhibited cell proliferation and Ki67/lncRNA-PVT1 expression levels while enhancing apoptosis and upregulating miR-361-3p and Bax and Cleaved-caspase-3. Co-treatment of AST-IV and BV enhanced the sensitivity of A549 cells to BV, further promoted apoptosis, and inhibited cell proliferation. Overexpression of lncRNA-PVT1 down-regulated miR-361-3p levels and partially reversed the promotional effect of AST-IV and BV on the sensitivity of A549 cells to BV. On the basis of overexpression of lncRNA-PVT1, upregulation of miR-361-3p expression significantly increased the sensitivity of A549 cells to BV. Binding interactions between lncRNA-PVT1 and miR-361-3p, as well as miR-361-3p and HMGB1, were confirmed through luciferase assays. Additionally, HMGB1 overexpression counteracted the suppressive effects of AST-IV and BV on A549 cell proliferation and resistance.

CONCLUSIONS

AST-IV increased miR-361-3p expression while suppressing HMGB1 via downregulation of lncRNA-PVT1, thereby enhancing BV sensitivity in NSCLC.