Di-san junyi daxue xuebao (Oct 2021)
Sorafenib combined with ophiopogonin D' inhibits ERK and AKT pathways to promote apoptosis in androgen-independent prostate cancer PC3 cells
Abstract
Objective To investigate the anti-tumor effect of sorafenib (Sor) combined with Ophiopogonin D'(OPD') on androgen-independent prostate cancer (PC3) cells and its mechanism. Methods In vitro, the expression of AKT, p-AKT, ERK and p-ERK in PC3 cells was detected by Western blotting in 24 h after being treated with different concentrations of OPD' (0, 1, 2.5 and 5.0 μmol/L), Sor (0, 2.5, 5.0 and 10.0 μmol/L) and OPD' (2.5 μmol/L)+Sor (5.0 μmol/L), respectively. Apoptosis of PC3 cells was observed by flow cytometry with AnnexinV-FITC and propidium iodide (PI) double staining. In vivo, PC3 cells xenograft tumor model was constructed in nude mice. Subsequently, 24 nude mice were equally divided into control group, OPD' group (1.0 mg/kg), Sor group (2.5 mg/kg) and OPD' +Sor combined group. The body weight of nude mice and the tumor volume were measured and recorded every 3 days until 21 d after drug intervention. Results Sor mainly down-regulated the expression levels of p-AKT and p-AKT/AKT (P < 0.05), and only decreased p-ERK/ERK level at the concentration of 10.0 μmol/L (P < 0.05). While OPD' primarily down-regulated p-ERK and p-ERK/ERK levels (P < 0.05), and only reduced p-AKT/AKT at 5.0 μmol/L (P < 0.05). However, the protein levels of p-AKT, p-ERK, p-AKT/AKT, and p-ERK/ERK were all greatly diminished in the combined group (2.5 μmol/L OPD' +5.0 μmol/L Sor) (P < 0.05). In addition, the apoptotic index was significantly higher in the combined group than the OPD' or Sor alone group (P < 0.05). The results of in vivo experiments also showed that the tumor volume and tumor weight in the combined group (1.0 mg/kg OPD' +2.5 mg/kg Sor) were much lower than those in the other groups (P < 0.05). Conclusion Sor combined with OPD' promotes apoptosis in PC3 cells by inhibiting ERK and Akt pathways.
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