Cytotoxic and photodynamic effects of Photofrin on sensitive and multi-drug-resistant Friend leukaemia cells.
To study cross-resistance to Photofrin (PF) photosensitization, a Friend leukaemia cell line (ADM-RFLC) with a high level of multi-drug resistance (MDR) and the parental sensitive cell line (FLC) have been used. PF uptake measured by HPLC shows a similar intracellular drug accumulation in both cell lines. The ID50s for cell growth inhibition by PF are also similar after exposure in the dark in the two cell lines, while after illumination they are slightly lower in ADM-RFLC than in FLC cells. Moreover, verapamil, known to reverse the MDR phenotype induced by P-glycoprotein over-expression (the drug efflux mechanism), affects equally ADM-RFLC and FLC cells sensitivity to PF. In addition, photodynamic treatment with PF did not reverse the resistance to rhodamine 123 and aclarubicin, but partly reverses resistance of ADM-RFLC cells to antitubulin drugs such as vinblastine or vincristine. These latter results could have clinical application in the treatment of tumours expressing the MDR phenotype.
Dellinger
M
M
Laboratoire de Biophysique, INSERM U201, CNRS URA 481, Muséum National d'Histoire Naturelle, Paris, France.
Moreno
G
G
Salet
C
C
Tapiero
H
H
Lampidis
T J
TJ
D000818:Animals; D004351:Drug Resistance; D017324:Hematoporphyrin Derivative / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D017324:Hematoporphyrin Derivative