MECHANISMS BEHIND THE RESISTANCE OF SPHEROIDS TO PHOTODYNAMIC TREATMENT: A FLOW CYTOMETRY STUDY

Authors

  • Catharine M. L. West,

    Corresponding author
    1. Cancer Research Campaign, Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Christie Hospital, Wilmslow Road, Manchester M20 9BX, UK
    Search for more papers by this author
  • James V. Moore

    1. Cancer Research Campaign, Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Christie Hospital, Wilmslow Road, Manchester M20 9BX, UK
    Search for more papers by this author

*To whom correspondence should be addressed.

Abstract

Abstract— The influence of cell heterogeneity on response to photodynamic treatment (PDT) has been investigated using the human colon adenocarcinoma line WiDr, grown as spheroids and exposed to hematoporphyrin derivative. The spheroids show a marked spheroid size-dependent resistance to PDT. Using a flow cytometer, cell sub-populations have been separated, on the basis of drug fluorescence, from single cell suspensions prepared from 500 μm diameter spheroids. Cells low in fluorescence have been shown to be resistant to PDT, have a smaller median cell volume, and be enhanced in G1-type cells. These cells also show reduced low density lipoprotein uptake. The results suggest that spheroid size-dependent resistance to PDT is related to a decreasing growth fraction with increasing spheroid size. Heterogeneity of drug uptake could be a potential limitation to clinical PDT.

Ancillary