The expression of BCRP/ABCG2 causes resistance to Photofrin^®-PDT

Abstract

It has been reported that efflux pump such as the transporter protein causes drug-resistance and exerts an unfavorable effect in relation to attenuate the anti-tumor activity of anti-cancer agents. Recently, it has been reported that porphyrin is a substrate of a member of ATP-binding cassette family, BCRP/ABCG2 (Breast cancer resistant protein). We hypothesized whether Photofrin^® and / or Laserphyrin^® was pumped from the cancer cells by BCRP protein, and the expression of BCRP may cause the resistance to the anti-tumor effect of PDT.
In this study, we evaluated the influence of the expression of BCRP on the anti-tumor effect of Photofrin^®-PDT or Laserphyrin^®-PDT using BCRP-overexpressing A431/BCRP cells in vitro. A431/BCRP cells were resistant to the anti-tumor effect of Photofrin^®-PDT as compared to the parental A431 cells by WST assay. Furthermore, we examined the other members of transporters containing ATP-binding cassette, MDR1 and MRP1. A431/MDR1 cells and KB3-1/MRP1 cells were a little resistant to the anti-tumor effect of Photofrin^®-PDT as compared to the parental cells by WST assay. The dose modifying factor at the IC50 of A431/BCRP was 1.83 and the highest among those cells. However, there was no difference of the anti-tumor effect of Laserphyrin^®-PDT between A431/BCRP cells and A431 cells. These results suggest that Photofrin^® is a substrate of BCRP but Laserphyrin^® is not.
In conclusion, the expression of BCRP can exert an unfavorable effect in relation to attenuate the anti-tumor effect of Photofrin^®-PDT.