Effects of a novel photoactivated photosensitizer on MDR1 over-expressing human breast cancer cells

Abstract

Multidrug resistance (MDR) was the main reason of cancer chemotherapy failure. Photodynamic therapy (PDT) has been applied to the treatment of tumor and considered as a strategy for the overcoming of MDR phenomenon. Present study focused on a novel porphyrin-based photosensitizer DTP (meso-5-[p-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin)-mediated photocytotoxicity on MDR1 highly expressing human breast cancer cell line MCF-7/ADR (adriamycin resistant) and the parental MCF-7 cell line. Experimental results indicated that DTP-PDT induced significant photocytotoxicity on MDR1 highly expressing MCF-7/ADR cell line, in spite of slightly weaker than on MCF-7 cell line, which was due to the relatively lower level of intracellular DTP in resistant MCF-7/ADR cells. Furthermore, intracellular DTP level in resistant MCF-7/ADR cells could not be altered with a Pgp inhibitor, verapamil and this indicated that DTP was not a possible substrate for the multidrug transporter Pgp. More importantly, photoactivated DTP could significantly reduce the expression of MDR1 gene at all the levels of mRNA, protein and function. The combined treatment with DTP-PDT and adriamycin was found to be more effective than adriamycin or DTP-PDT alone. In conclusion, our data demonstrated that DTP probably will be a potential photosensitizer in combating MDR phenomenon during the treatment of human breast cancer.