Experimental study of a novel photosensitizer mediated photodynamic therapy on resistant gastric cancer / 中国药理学通报

ABSTRACT

Aim To investigate the therapeutic efficacy of DTP-mediated photodynamic therapy (PDT) on SGC7901/VCR human vincristine ( VCR )-resistant gastric cancer cells, and to reveal the relationship between DTP-PDT and P-gp. Methods MTT assay was employed to evaluate the cytotoxicity of DTP-PDT and combination treatment with DTP-PDT and VCR. A SGC7901/VCR-bearing nude mouse model was established, and the tumor volume was measured to draw the growth curve. Cell apoptosis was detected by flow cytometry, and the yield of intracellular singlet oxygen (O2) was determined after DTP-PDT. The expression of MDR1 mRNA and P-gp was determined by qPCR and flow cytometry, respectively. Results DTP-PDT demonstrated significant cytotoxicity on SGC7901/VCR cells and the nude mice transplanted tumor. DTP-PDT could induce the apoptosis of SGC7901/VCR cells and the generation of intracellular O2. DTP-PDT could inhibit the expression of MDR1 mRNA and P-gp, which could be reduced by a-tocopherol. Combined treatment with DTP-PDT and VCR demonstrated synergistic efficacy on resistant cells, which could be reduced by or-tocopherol. Conclusions O2 generated by DTP-me-diated PDT could inhibit the growth of SGC7901/VCR cells and induce cell apoptosis. Meanwhile, it inhibits the over-expression of P-gp on cell membranes, leading to reduced efflux of VCR and synergistic efficacy with DTP-PDT and VCR eventually.