Nrf2 Is Involved In The Resistant To Mppa-PDT In Human Ovarian Cancer Cells

Objective:To observe the effect of Mppa-PDT on human ovarian cancer by down regulating Nrf2, and to explore the mechanism of Nrf2 in the treatment of human ovarian cancer cell line resistant to photodynamic therapy.Methods : Ovarian cancer cell line A2780 and SKOV3 in the logarithmic phase were randomized in groups,and the siRNA transfection and Mppa-PDT treatment were carried out.Then cell viability were measured by CCK-8 assay, cellular apoptosis were detected with annexin V / PI double staining flow cytometry, the level of intracellular reactive oxygen species(ROS) were tested by DCFH-DA staining, the accumudation of Mppa were observed with flow cytometry and fluorescence microscope,the transcription of Nrf2 were observed with immunofluorescence method, the expression of Nrf2、ABCG2、HO-1、NQO1 were detected by Western Blot.Results:1. Mppa-PDT can inhibit cell viability and induce apoptosis in human ovarian cancer cells.2. Mppa-PDT can activate Nrf2.3. The effect of Mppa-PDT on human ovarian cancer cells is enhanced by NRF2 down regulation.4. ROS level induced by Mppa-PDT can be levated by Nrf2 down-regulation.5. Increasing ROS result from increased Mppa accumulation by Nrf2-ABCG2 inhibition in SKOV3 cells or decreased antioxidant by Nrf2-H0-1 inhibition in A2780 cells.6. P-Nrf2 and ABCG2 was involved in the resistance to Mppa-PDT in SKOV3 cells.Conclusion:The enhancement of Methyl Pyropheophorbide-a mediate photodynamic therapy effect was achieved through ROS increasing by inhibiting Nrf2-HO-1 or Nrf2-ABCG2 signaling...