Curcumin reverses resistance of human esophageal cancer Eca-109/VCR cells to vincristine by inhibiting Notch1 signaling pathway / 肿瘤

ABSTRACT

Objective: To investigate the reversal effect of curcumin (Cur) on the resistance of human esophageal cancer Eca-1 09/vincristine (VCR) cells to VCR, and to explore its possible mechanism. Methods: MTT method was used to detect the effect of different concentrations of Cur on the proliferation of Eca-1 09/VCR cells and the reversal effect of Cur (25 μmol/L) on the resistance of Eca-109/VCR cells to VCR. The Eca-109/VCR cells were treated with Cur (25 μmol/L) alone, VCR (2 μg/mL) alone or Cur (25 μmol/L) combined with VCR (2 μg/mL) for 24 h, respectively. Then the apoptosis was analyzed by FCM and Hoechst 33258 fluorescence staining. The expression levels of Notch1, Jagged1, and hairy and enhancer of split 1 (Hes1) mRNAs were detected by real-time fuorescent quantitative PCR. The expressions of Notch1, Jagged1, Hes1 and P-glycoprotein (P-gp) proteins were measured by Western blotting. Results: The proliferation inhibitory rate of Eca-1 09/VCR cells was (8.82±0.80) % after the treatment with 25 μmol/L Cur. After the treatment with Cur (25 μmol/L) and various concentrations of VCR for 24 h, the half maximal inhibitory concentration (IC50) of VCR on Eca-1 09/VCR cells is decreased from (7.70±0.63) μg/mL to (2.55± 0.12) μg/mL. The reversal fold of Cur was 3.02. After the treatment with Cur (25 μmol/L) and VCR (2 μg/mL) for 24 h, the apoptosis rate of Eca-1 09/VCR cells was significantly higher than those in Cur (25 μmol/L) group and VCR (2 μg/mL) group (both P < 0.05), the expression levels of Notch1, Jagged1 and Hes1 mRNAs were significantly lower than those in Cur (25 μmol/L) group and VCR (2 μg/mL) group (all P < 0.01), and the expressions of Notch1, Jagged1, Hes1 and P-gp proteins were significantly down-regulated in Eca-1 09/VCR cells (all P < 0.05). Conclusion: Cur can obviously reverse the resistance of esophageal cancer Eca-109/VCR cells to VCR. The mechanism may be related to the inhibition of Notch1 signaling pathway and the down-regulation of P-gp expression.