The Role Of ABCG2 In The Sensitivity Of Glioma To Methy1 Pyropheophorbide-a-mediated Photodynamic Therapy

Background and Objective: 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 efflux of anticancer drugs.The purpose of this study was to investigate the mechanisms of human glioblastoma sensitivity to methyl ester pyropheophorbide-a(MPPa)-mediated photodynamic therapy(PDT)eradicate tumour cells and the relationship with ABCG2.Materials and Methods: U87,A172,SHG-44 and U251 glioma cell lines in the logarithmic growth phase were selected and exposed to the treatment of Mppa-PDT.The cell viability was measured with the use of CCK-8 assay;the m RNA expression of ATP-binding cassette transporters(ABCG2,MRP1 and MDR1)were detected by PCR;the expressions of ABCG2 and intracellular contents of Mppa in four glioma cell lines was detected with Western Blot and flow cytometry respectively.Then the cell line,which was relatively insensitive to Mppa-mediated PDT,was chosen in the next experiment.The insensitive cells were divided into 4 groups.They were Illuminated group(group A),FTC + Illumination group(group B),Mppa-PDT group(group C)and Mppa-PDT + FTC group(group D).Cell viability was measured by CCK-8 assay.Apoptotic rate,intracellular contents of Mppa in each group without illumination and level of ROS among the four groups were detected by the use of flow cytometry.Results: The viabilities of the four GBM cell lines decline after MPPa-PDT in a radiant exposure-dependent manner.The viabilities of A172 cells were higher compared to other cell lines;Following the incubation with MPPa at 2?M/L for 12 h,the intracellular MPPa are significantly lower in A172 and SHG-44 cells than that in U251 and U87(P=0.0000);Both the m RNA and protein expression level of ABCG2 in A172 are significantly highest among the four GBM cells(P=0.0000);Inhibition of ABCG2,the intracellular MPPa in FTC+Mppa group are higher than that Mppa group(P<0.0001);The level of ROS was improved in group D compared with group C(P<0.0001).The cell viability of group D treated by Mppa-mediated PDT was significantly lower than that of group C(P<0.001).The cell apoptotic rate increased significantly in group D compared to group C(P<0.001).Conclusions: ABCG2 plays a significant role in the resistance of A172 to MPPa-PDT.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 cell through efflux of Mppa,resulting in decline of cytotoxicity.