title: The ABCG2 transporter is a key molecular determinant of the efficacy of sonodynamic therapy with Photofrin in glioma stem-like cells.
abstract: We aimed to investigate the role of the ABCG2 transporter in the efficacy of sonodynamic therapy (SDT) with Photofrin in the glioma stem-like cells (GSCs) isolated and cultured from U251 glioma cells. Immunocytochemistry and flow cytometry analyses showed that ABCG2 was overexpressed in GSCs, and the percentage of ABCG2-positive GSCs was approximately 100%. The effect of ABCG2 on Photofrin extrusion in the absence or presence of a specific inhibitor of ABCG2 (fumitremorgin C; FTC) was investigated by determining the intracellular concentration of Photofrin in GSCs incubated with 20μg/ml Photofrin. Extrusion of Photofrin by ABCG2 was inhibited by 10μM FTC, which significantly increased the intracellular Photofrin concentration (p<0.05) from 0.32±0.11μg/10(6) cells to 0.89±0.13μg/10(6) cells. MTT and TUNEL assays showed that the antitumor effect of SDT (incubation of GSCs with 20μg/ml Photofrin for 6h in the dark and ultrasonic activation at 1.0MHz and 0.5W/cm(2) for 2min) was significantly improved by FTC pretreatment (p<0.05). Moreover, incubation of GSCs with FTC significantly increased the relative production of ROS in response to SDT. The overexpression of ABCG2 in GSCs results in efflux of Photofrin, indicating that the antitumor effect of SDT with Photofrin may be reduced in GSCs overexpressing ABCG2. However, since FTC improves the efficacy of SDT in GSCs by inhibiting ABCG2-mediated efflux of Photofrin, FTC may be useful in SDT treatment of ABCG2-expressing cancer cells.
authors: Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing University of Medical Science, Chongqing 400010, China.
authors: Zhong-Ye
authors: ZY
authors: Xu
authors: Kai
authors: K
authors: Wang
authors: Xiao-Qing
authors: XQ
authors: Li
authors: Song
authors: S
authors: Chen
authors: Jin-Mu
authors: JM
authors: Deng
authors: Yuan
authors: Y
authors: Cheng
authors: Zhi-Gang
authors: ZG
authors: Wang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D017323:Dihematoporphyrin Ether / Q000494:pharmacology*; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000502:physiology*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D017323:Dihematoporphyrin Ether