Pyropheophorbide-a methyl ester-mediated photodynamic therapy induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress pathway
Zhu Jiang,Chen Qing,Tian Si,Jia Gongwei,Bai Dingqun,Yu Lehua.Pyropheophorbide-a methyl ester-mediated photodynamic therapy induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress pathway[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(21):2115-2120.
Zhu Jiang,Chen Qing,Tian Si,Jia Gongwei,Bai Dingqun,Yu Lehua.Pyropheophorbide-a methyl ester-mediated photodynamic therapy induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress pathway[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(21):2115-2120.DOI:
Objective To investigate the mechanism of endoplasmic reticulum stress pathway in pyropheophorbide-a methyl ester (MPPa)-mediated photodynamic therapy (PDT) in inducement of breast cancer cells apoptosis
. Methods The MCF-7 cells were randomly divided into the MPPa-PDT group and 3 control groups (the blank control group
the MPPa alone group
and the light alone group). The cells were co-cultured with MPPa at different concentrations (0
0.5
1
2 and 4 μmol/L) and exposed to the light of different energy intensities (0
0.9
1.8
2.7 and 3.6 J/cm
2
). CCK-8 assay was used to measure the viability of MCF-7 cells. Confocal laser scanning with ER-tracker GREEN Probe uploading was used to observed the subcellular location of MPPa (2 μmol/L). When the cells were treated with 2 μmol/L MPPa and exposed to 1.8 J/cm
2
light
flow cytometry with Annexin V-FITC/PI double-staining was used to assess the cell apoptosis. Flow cytometry with Flou-3/AM was used to measure the concentrations of free calcium ion in the cells. Western blotting was used to detect the protein levels of endoplasmic reticulum stress marker BIP
and its related apoptotic proteins
CHOP and caspase-12. Results Cell proliferation of MCF-7 cells was significantly inhibited by MPPa-PDT in an energy-dependent manner (P0.05). MPPa was enriched in the endoplasmic reticulum. Flow cytometry showed the apoptotic rate and the Ca
2+
level were obviously higher in the MPPa-PDT treated cells than the control cells (P0.05). Western blot analysis indicated that the expression levels of BIP
CHOP and caspase-12 were increased in the MPPa-PDT group at all time points
whereas those in the control groups were low. Conclusion MPPa-PDT induces apoptosis in the MCF-7 cells through endoplasmic reticulum stress pathway.