Inhibiting ABCG2 could potentially enhance the efficacy of Hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer

Publication date: Available online 30 June 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): M. Ibrahim Khot, Sarah L. Perry, Thomas Maisey, Gemma Armstrong, Helen Andrew, Thomas A. Hughes, Nikil Kapur, David G. Jayne
BackgroundPhotodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids.MethodsSpheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 hours. Cultures were irradiated with light (1 J/cm²) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated.ResultsHypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01).ConclusionsHypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which maybe attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT maybe enhanced by ABCG2 inhibition.



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