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Updated: May 9, 2026
An In Vitro Approach to Photodynamic Therapy
Published on: August 17, 2018
Differential sensitivity in cell lines to photodynamic therapy in combination with ABCG2 inhibition
Gemma A Barron1, Harry Moseley, Julie A Woods
1Photobiology Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland DD1 9SY, United Kingdom. g.a.barron@dundee.ac.uk
Background:
ABCG2 is an ATP-binding cassette transporter protein which has a role in the regulation of endogenous protoporphyrin IX (PpIX) levels.
Objective:
To understand the influence of ABCG2 on porphyrin-based photodynamic therapy (PDT) and fluorescence diagnosis (FD), we examined the role of endogenous ABCG2 in four human cell lines from the epidermis (HaCaT keratinocytes), oesophagus (OE19 adenocarcinoma), brain (SH-SY5Y neuroblastoma) and bladder (HT1197 carcinoma).
Methods:
Cells were incubated with ALA or MAL in the presence or absence of the ABCG2 activity inhibitor Ko-143. Porphyrin accumulation was detected by spectrofluorimetric analysis and high performance liquid chromatography (HPLC) with porphyrin localisation observed by confocal laser scanning microscopy. PDT efficacy was assessed 24h post irradiation (1.5J/cm(2) red light) by the neutral red (NR) assay.
Results:
We show cell-specific differences when Ko-143 was co-incubated with ALA or, in particular with, MAL. Enhanced PDT-induced cell kill was shown in HaCaT, OE19 and HT1197 cells, but not SH-SY5Y cells and could be explained by porphyrin accumulation and expression of ABCG2. We have also found that despite high levels of intracellular PpIX, the OE19 cells were protected from phototoxic cell death by PpIX compartmentalisation. This could be reversed by Ko-143.
Conclusion:
The results from this study show a possible cause of reduced sensitivity to ALA/MAL-PDT, with a potential solution to overcome this effect in certain tissue types. The potential to improve PDT with Ko-143 remains promising.
Insights
The ATP-binding cassette transporter ABCG2 influences photodynamic therapy (PDT) efficacy. Inhibiting ABCG2 with Ko-143 enhances PDT in certain cell types, offering a potential strategy to improve treatment outcomes.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- ABCG2, an ATP-binding cassette transporter, regulates endogenous protoporphyrin IX (PpIX) levels.
- ABCG2 plays a role in the efficacy of photodynamic therapy (PDT) and fluorescence diagnosis (FD).
Purpose of the Study:
- To investigate the influence of ABCG2 on porphyrin-based PDT and FD.
- To examine the role of endogenous ABCG2 in various human cell lines (epidermis, oesophagus, brain, bladder).
Main Methods:
- Cells were treated with ALA or MAL, with or without the ABCG2 inhibitor Ko-143.
- Porphyrin accumulation was quantified using spectrofluorimetry and HPLC.
- PDT efficacy was assessed via cell viability assays after red light irradiation.
Main Results:
- Cell-specific differences in response to ABCG2 inhibition were observed.
- Inhibition of ABCG2 with Ko-143 enhanced PDT-induced cell kill in HaCaT, OE19, and HT1197 cells.
- PpIX compartmentalization protected OE19 cells from phototoxicity, an effect reversed by Ko-143.
Conclusions:
- ABCG2 activity is a potential factor in reduced sensitivity to ALA/MAL-PDT.
- Inhibiting ABCG2 with Ko-143 may offer a method to overcome resistance and improve PDT outcomes in specific tissues.
- The use of Ko-143 shows promise for enhancing PDT efficacy.
