RRC ID 43898
Author Zhao SG, Chen XF, Wang LG, Yang G, Han DY, Teng L, Yang MC, Wang DY, Shi C, Liu YH, Zheng BJ, Shi CB, Gao X, Rainov NG.
Title Increased expression of ABCB6 enhances protoporphyrin IX accumulation and photodynamic effect in human glioma.
Journal Ann Surg Oncol
Abstract BACKGROUND:Glioma recurrence usually occurs close to the tumor resection margins as a result of residual infiltrating glioma cells. 5-aminolevulinic acid (ALA) fluorescence-guided resection of gliomas has been demonstrated to enhance discrimination of tumor tissue and to improve survival. ALA-based photodynamic therapy is an effective albeit still experimental adjuvant treatment option for gliomas. However, insufficient protoporphyrin IX (PpIX) accumulation may limit the benefits of fluorescence-guided resection and photodynamic therapy.
METHODS:We investigated the expression of the ATP-binding cassette transporter ABCB6, which regulates porphyrin synthesis, in surgical specimens from human gliomas and manipulated ABCB6 in human glioma cell lines.
RESULTS:Our findings demonstrated that expression levels of ABCB6 were greatly elevated in human gliomas compared with normal brain tissues and correlated with World Health Organization histologic grade. A previously undescribed finding was that ABCB6 mRNA expression in solidly fluorescing tumor tissues was higher than that in vaguely fluorescing tumors, suggesting that ABCB6 may be at least in part responsible for PpIX accumulation in glioma cells. Accordingly, ABCB6 overexpression in glioma cell lines caused a marked increase in intracellular levels of PpIX, and was more sensitive to ALA-induced photodynamic therapy-events that could be prevented by silencing ABCB6 via siRNA treatment.
CONCLUSIONS:Our findings indicate a crucial role of ABCB6 in ALA metabolism and accumulation of PpIX in glioma. ABCB6 overexpression is a potential approach to enhance accumulation of PpIX for optimizing the subjective discrimination of vague fluorescence and improving the efficacy of ALA-based photodynamic therapy.
Volume 20(13)
Pages 4379-88
Published 2013-12-1
DOI 10.1245/s10434-011-2201-6
PMID 22688660
MeSH ATP-Binding Cassette Transporters / antagonists & inhibitors ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Aminolevulinic Acid / pharmacology* Apoptosis Blotting, Western Brain / metabolism* Brain Neoplasms / genetics Brain Neoplasms / metabolism* Brain Neoplasms / prevention & control Case-Control Studies Cell Proliferation Fluorescence Glioma / genetics Glioma / metabolism* Glioma / prevention & control Humans Light Photochemotherapy* Photosensitizing Agents / pharmacology Protoporphyrins / metabolism* RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured
IF 4.061
Times Cited 39
Human and Animal Cells U251(RCB0461) T98G(RCB1954)