Combination of Platycodin D with docetaxel synergistically suppressed cell growth in DU-145 by enhancing apoptosis and alleviating autophagy.

Since the side effects and chemo-resistance of docetaxel (DTX) limit its anticancer performance in treating castration-resistant prostate cancer (CRPC), many studies have attempted to identify novel combination treatment to meet clinical needs. Platycodin D (PD), a natural component from Platycodon grandiflorus(Jacq.) A.DC. appears to inhibit proliferation in many cancers. This study investigated the effect of combining PD and DTX in DU-145 cells and explored its underlying mechanism. Anti-proliferation activity was detected by MTT assay. The combination index (CI) was calculated to elucidate the synergistic effect of PD and DTX. DAPI and Annexin V-FITC/PI staining were used to observe the apoptosis. To monitor autophagy flux, Ad-mCherry-GFP-LC3 was conducted. Flow cytometry was employed to investigate the production of reactive oxygen species (ROS) and the expression levels of proteins were analyzed by western blot. Results showed that PD and DTX combination treatment synergistically inhibited cell growth. Annexin-V/PI staining demonstrated that combination treatment enhanced apoptosis, accompanied with the upregulation of cleaved PARP, cleaved caspase-3/9 and Bax/Bcl-2 ratio. Additionally, PD and DTX together inhibited autophagy with the downregulation of related proteins compared with PD group. Flow cytometry indicated that the combination group promoted ROS production, increased the expression of p-P38 (Thr180/Tyr182), decreased the expression of p-EGFR and suppressed its downstream Akt/mTOR and ERK pathways. Briefly, PD combined with DTX showed significant synergism on DU-145 cells with enhanced apoptosis and alleviated autophagy, suggesting that PD could decrease the dosage and side effects of DTX and optimize its clinical use for prostate cancer. [ABSTRACT FROM AUTHOR]