Deferoxamine-sensitized 5-Aminolevulinic acid photodynamic therapy for breast cancer
Objective To study the synergistic effect of deferoxamine(DFO)on 5-Aminolevulinic acid(5-ALA)photodynamic therapy of breast cancer in vivo and in vitro and its mechanism.Methods The laboratory subcultured human breast cancer cell line MCF-7 was used as the model cell,and female BALB/c nude mice were used as the model animals.First,the confocal microscope was used to investigate the effects of DFO on the level of intracellular iron ions and the transformation of 5-ALA in cells.A series of experiments were conducted to investigate the enhanced conversion of photosensitizer protoporphyrin Ⅸ(PpⅨ),apoptosis,and DNA damage sensitization by DFO.Finally,the inhibitory effect of DFO-en-hanced 5-ALA photodynamic therapy on the proliferation of MCF-7 cells was verified in vivo.T-tests was used for comparison between groups.Results The degree of DNA damage in the 5-ALA DFO group was severer than that in the 5-ALA group and the DFO group.DFO significantly increased the level of PpⅨ,the active intermediate of 5-ALA in MCF-7 cells,increased the production of reactive oxygen species(ROS),down-regulated the level of intracellular iron ions,effectively blocked DNA repair,and then in-creased the damage to intracellular DNA(tailing value of 26％,and there was almost no tailing in other groups).The cell viability rate of the 5-ALA+DFO group was(58.83±2.41)％,significantly lower than that of the 5-ALA group[(76.17±2.54)％,t=11.06,P＜0.01].The ratio of dead cells to live cells in the 5-ALA+DFO group(0.79±0.03)was significantly higher than that in the control group,the 5-ALA group and the DFO group(0.10±0.02,0.40±0.03,0.28±0.05,t=45.44,22.30,21.83,P＜0.01).The apoptosis ratio of the 5-ALA+DFO group was(26.47±1.42)％,which was significantly higher than that of the control group,the 5-ALA group,and the DFO group[(6.65±0.49)％,(12.22± 1.03)％,(11.47±0.59)％,t=29.49,17.37,21.83,P＜0.01).DFO can significantly reduce cell viability(cell survival rate of only 30％,P＜0.01),significantly induce apoptosis of tumor cells(apopto-sis rate of 25.8％,P＜0.01),and inhibit the proliferation and growth of tumor cells.In the nude mouse xenograft model,the tumor weight of the 5-ALA DFO group was significantly lower than that of the control,5-ALA and DFO groups.DFO can effectively inhibit the proliferation of MCF-7 nude mouse xenograft in vi-vo and exhibit low toxicity and side effects.Conclusion DFO can effectively sensitize 5-ALA photody-namic therapy and inhibit tumor cell proliferation.
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