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Arctigenin-induced reversal of drug resistance in cisplastin-resistant cell line A549/DDP, and the mechanism involved
Abstract
Purpose: To investigate the drug resistance reversal effect of arctigenin (ARG) on cisplatin-insensitive A549/DDP cancer cells, and to elucidate the underlying mechanism(s).
Methods: Four groups of cells: control, DDP, ARG and ADP were used. The degrees of inhibition of proliferation, drug resistance and apoptotic changes were measured using MTT assay, CCK-8 assay and flow cytometry, respectively. Expressions of PTEN and STAT3 proteins were determined by Western blotting.
Results: At ARG concentration of 5 μmol/L, A549/DDP cells were significantly inhibited (p < 0.05). The combination therapy was more effective in reversing A549/DDP cells resistance than the single therapy. The expression level of PTEN protein increased with increase in ARG concentration, while STAT3 protein expression decreased with increase in ARG concentration. ADP group up-regulated PTEN but decreased STAT3 expression levels.
Conclusion: ARG regulates drug resistance in A549/DDP cells, possibly via a mechanism involving reduction of A549/DDP cell sensitivity to DDP, thereby regulating the stress pathways associated with PTEN and STAT3. The combination of ARG and DDP effectively reduces A549/DDP cells resistance.
