Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers

BMC Cancer

Research Article

Yoon Jin Roh¹  Ju Hee Kim¹  In-Wook Kim¹  Myung-Gyu Choi¹  Jae Myung Park²  Tayyaba Hasan³ 

[1] Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea;Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea;Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 137-071, Seoul, South Korea;Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;

关键词: Photodynamic therapy;    Colon cancer;    Protoporphyrin;    ATP-binding cassette transporters;    Photosensitizing agents;   

DOI  :  10.1186/s12885-015-1514-4

 received in 2014-12-27, accepted in 2015-06-25,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPhotodynamic therapy (PDT) contains a photosensitizing process, which includes cellular uptake of photosensitizer and delivery of light to the target. ATP-binding cassette subfamily G2 (ABCG2) regulates endogenous protoporphyrin levels. In human colon cancers, it is not fully examined the role of ABCG2 in porphyrin-based photodynamic therapy.MethodsSW480 and HT29 cells were selected because they showed low and high ABCG2 expression levels, respectively. Pyropheophorbid-a (PPa) was used as a photosensitizer. Cells were exposed to a 670 nm diod laser. Cell viability and necrosi apoptosis was examined. Production level of singlet oxygen was detected with the photomultiplier-tube s/ -based singlet oxygen detection system.ResultsSW480 cells, which expressed lower level of ABCG2, showed the higher uptake of PPa than HT-29 cells. The uptake level of PPa was significantly correlated with the decreased cell viability after PDT. Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells. To confirm the ABCG2 effect on PDT, we established ABCG2 over-expressing stable cells in SW480 cells (SW480/ABCG2). Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells. The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT.ConclusionABCG2 plays an important role in determining the PDT efficacy by controlling the photosensitizer efflux rate. This implies the control of ABCG2 expression may be a potential solution to enhance photosensitivity.

【 授权许可】

Unknown   
© Kim et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.