Si Tian 1 , Min Yong 2 , Jiang Zhu 3 , Li Zhang 1 , Li Pan 1 , Qing Chen 1 , Kai-Ting Li 1 , Yu-Han Kong 1 , Yuan Jiang 3 , Ting-He Yu 2 , Le-Hua Yu 3 , Ding-Qun Bai 1 Show Affiliations »
Abstract
BACKGROUND: Emerging evidence indicates that the transcription factor nuclear factor-E2-related factor 2 (Nrf2) plays an essential role in cellular defense against oxidative stress; its activation has been related to cytoprotection. OBJECTIVE: Here, we investigated the role of Nrf2 in improving the efficacy of methyl pyropheophorbide-amediated photodynamic therapy (Mppa-PDT) via the downregulation of Nrf2. METHOD: Human ovarian cancer A2780 cells and SKOV3 cells were treated with Mppa-PDT and siRNA transfection was performed to inhibit Nrf2. After treated with siRNA and Mppa-PDT, the cell viability was examined with CCK-8 assay; cell apoptosis was detected tested by flow cytometry with Annexin V-FITC/PI; the celluar reactive oxygen species (ROS) and mitochondrial membrane potential were measured with DCFHDA and JC-1 staining; expression of protein was assessed by western blot analysis. RESULTS: We found that Nrf2 translocated from the cytoplasm to the nucleus in vitro and in vivo, and the expression of Nrf2 and P-Nrf2 increased through a possible mechanism regulated by mitogen-activated protein kinase (MAPK) after Mppa-PDT treatment. Furthermore, cytotoxicity and apoptosis induced by Mppa-PDT increased after Nrf2down-regulation. Nrf2 down -regulation increased reactive oxygen species (ROS) levels by attenuating antioxidants or pumping Mppa out of cells,which resulted from the inhibition of Nrf2-HO-1 or Nrf2- ABCG2 signaling. In addition, SKOV3 cells exhibited increased resistance to Mppa-PDT, and the expression levels of P-Nrf2 and ABCG2 were higher in SKOV3 cells than in A2780 cells, suggesting that Nrf2-ABCG2 signaling might be involved in the intrinsic resistanceto Mppa-PDT. CONCLUSION: These results provided evidence that Nrf2 down-regulation can enhance the effect of Mppa-PDT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
BACKGROUND: Emerging evidence indicates that the transcription factor nuclear factor-E2-related factor 2 (Nrf2 ) plays an essential role in cellular defense against oxidative stress; its activation has been related to cytoprotection. OBJECTIVE: Here, we investigated the role of Nrf2 in improving the efficacy of methyl pyropheophorbide-amediated photodynamic therapy (Mppa -PDT) via the downregulation of Nrf2 . METHOD: Human ovarian cancer A2780 cells and SKOV3 cells were treated with Mppa -PDT and siRNA transfection was performed to inhibit Nrf2 . After treated with siRNA and Mppa -PDT, the cell viability was examined with CCK-8 assay; cell apoptosis was detected tested by flow cytometry with Annexin V -FITC/PI; the celluar reactive oxygen species (ROS ) and mitochondrial membrane potential were measured with DCFHDA and JC-1 staining; expression of protein was assessed by western blot analysis. RESULTS: We found that Nrf2 translocated from the cytoplasm to the nucleus in vitro and in vivo, and the expression of Nrf2 and P-Nrf2 increased through a possible mechanism regulated by mitogen-activated protein kinase (MAPK) after Mppa -PDT treatment. Furthermore, cytotoxicity and apoptosis induced by Mppa -PDT increased after Nrf2down-regulation. Nrf2 down -regulation increased reactive oxygen species (ROS ) levels by attenuating antioxidants or pumping Mppa out of cells,which resulted from the inhibition of Nrf2 -HO-1 or Nrf2 - ABCG2 signaling. In addition, SKOV3 cells exhibited increased resistance to Mppa -PDT, and the expression levels of P-Nrf2 and ABCG2 were higher in SKOV3 cells than in A2780 cells, suggesting that Nrf2 -ABCG2 signaling might be involved in the intrinsic resistanceto Mppa -PDT. CONCLUSION: These results provided evidence that Nrf2 down-regulation can enhance the effect of Mppa -PDT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Entities: Chemical
Disease
Gene
Species
Keywords:
ABCG2; HO-1; Nrf2; P-Nrf2; PDT; ROS
Mesh： See more »
Substances： See more »
Year: 2017
PMID： 28356018 DOI： 10.2174/1871520617666170327145857
Source DB: PubMed Journal: Anticancer Agents Med Chem ISSN： 1871-5206 Impact factor: 2.505