The role of ABCG2 in the sensitivity of glioma to pyropheophorbide-amethyl ester-mediated photodynamic therapy
10.19401/j.cnki.1007-3639.2017.02.001
- VernacularTitle:胶质瘤对MPPa-PDT敏感性研究中ABCG2的作用
- Author:
Li PAN
;
Si TIAN
;
Li ZHANG
;
Haidan LIN
;
Hui GOU
;
Qing CHEN
;
Kaiting LI
;
Dingqun BAI
;
Yuhan KONG
;
Yunsheng OU
;
Lehua YU
- Keywords:
Adenosine triphosphate-binding cassette superfamily G member 2;
Pyropheophorbide-a methyl ester;
Photodynamic therapy;
Sensitivity;
Glioma
- From:
China Oncology
2017;27(2):81-88
- CountryChina
- Language:Chinese
-
Abstract:
Background and purpose:Adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2), which has been found over-expressed in a variety of cancer cells, takes part in the drug resistance of cancer through effux of anticancer drugs. The purpose of this study was to investigate the mechanisms of human glioblastoma cells sensitivity to pyropheophorbide-a methyl ester (MPPa)-mediated photodynamic therapy (PDT) eradicating tumour cells and its relationship to ABCG2.Methods:U87 and A172 glioma cell lines in the logarithmic growth phase were selected and exposed to the treatment of MPPa-PDT and MPPa-PDT+fumitremorgin C (FTC) respectively. The cell viability was measured with the use of CCK-8 assay. The expression of ABCG2 was detected by Western blot. The intracellular contents of MPPa in each group without illumination were tested by lfow cytometry. Flow cytometry with AnnexinⅤ-FITC/PI double staining was used to detect the cell apoptotic rate. DCFH-DA staining was used to assess the generation of intracellular reactive oxygen species (ROS).Results:The MPPa-mediated PDT could eradicate A172 and U87 cancer cells in an energy-dependent manner. The light energy density in A172 was 8 times of that in U87 when the cell viability reached median lethal dose after MPPa-mediated PDT. The high expression of ABCG2 in A172 cells affected the accumulation of intracellular MPPa. Inhibition of ABCG2, not only could enhance the eradicating effect of MPPa-PDT on A172 cells, but also could increase the yield of ROS triggered by MPPa-PDT and the accumulation of intracellular MPPa.Conclusion:The human glioblastoma cell line A172 is insensitive to MPPa-mediated PDT. The mechanism may relate to ABCG2, which decreases the MPPa content in cancer cells through effux of MPPa, resulting in decline of cytotoxicity.
