Effectiveness of lapatinib for enhancing 5 ‐aminolevulinic acid‐mediated protoporphyrin IX fluorescence and photodynamic therapy in human cancer cell lines with varied ABCG2 activities

Lapatinib, a repurposed ABCG2 inhibitor, dose-dependently enhanced ALA-induced PpIX fluorescence and PDT response in a panel of human tumor cell lines with varied ABCG2 activities and protein levels. Tumor cell lines with lower ABCG2 activities were more sensitive to lapatinib for PpIX/PDT enhancement. Abstract5-Aminolevulinic acid (ALA) is a prodrug for protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) and fluorescence-guided tumor surgery. We previously reported that lapatinib, a repurposed ABCG2 inhibitor, enhanced ALA-induced PpIX fluorescence and PDT by blocking ABCG2-mediated PpIX efflux. In the present study, we evaluated how the variation in ABCG2 activities/protein levels affected tumor cell response to the enhancement of PpIX/PDT by lapatinib and Ko143, an ABCG2 tool inhibitor. ABCG2 activities and protein levels were determined in a panel of human cancer cell lines. Effects of lapatinib and Ko143 on enhancing ALA-PpIX fluorescence and PDT were evaluated and correlated with tumor cell ABCG2 activities. We found that both lapatinib and Ko143 enhanced ALA-PpIX fluorescence and PDT in a dose-dependent manner, although lapatinib exhibited lower efficacy and potency than Ko143 in nearly all cancer cell lines. The EC50 of ABCG2 inhibitors for enhancing ALA-PpIX and PDT had a positive correlation with tumor cell ABCG2 activities, indicating that tumor cell lines with lower ABCG2 activities were more sensitive to ABCG2 inhibitors for PpIX/PDT enhancement. Our res...
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: SPECIAL ISSUE RESEARCH ARTICLE Source Type: research