Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers.

Abstract

BACKGROUND:

Photodynamic 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.

METHODS:

SW480 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.

RESULTS:

SW480 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.

CONCLUSION:

ABCG2 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.

• Authors: Ju Hee Kim, Jae Myung Park, Yoon Jin Roh, In-Wook Kim, Tayyaba Hasan, Myung-Gyu Choi
• Journal: BMC cancer (BMC Cancer) Vol. 15 Pg. 504 (Jul 07 2015) ISSN: 1471-2407 [Electronic] England
• PMID: 26149077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester
• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Diketopiperazines
• Heterocyclic Compounds, 4 or More Rings
• Neoplasm Proteins
• RNA, Messenger
• Adenosine

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (antagonists & inhibitors, genetics, metabolism)
• Adenosine (analogs & derivatives, pharmacology)
• Animals
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, genetics, metabolism, pathology)
• Diketopiperazines
• Disease Models, Animal
• Gene Expression
• Heterocyclic Compounds, 4 or More Rings
• Humans
• Male
• Mice
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• Photochemotherapy
• RNA, Messenger (genetics, metabolism)
• Tumor Burden
• Xenograft Model Antitumor Assays