کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6154842 | 1246344 | 2015 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Comparison between endothelial and tumor cells in the response to verteporfin-photodynamic therapy and a PI3K pathway inhibitor Comparison between endothelial and tumor cells in the response to verteporfin-photodynamic therapy and a PI3K pathway inhibitor](/preview/png/6154842.png)
- Verteporfin is localized in mitochondria in SVEC endothelial and PC-3 tumor cells.
- PC-3 cells have higher cellular uptake of verteporfin than SVEC cells.
- PC-3 cells show higher anti-apoptotic Bcl-2 family protein level than SVEC cells.
- SVEC cells are more sensitive to verteporfin-PDT and LY294002 than PC-3 cells.
- PDT and LY294002 sensitize SVEC cells, but not PC-3 cells, to undergo apoptosis.
BackgroundPhotodynamic therapy (PDT) is an established cancer treatment. Molecular-targeted agents targeting phosphatidylinositol 3-kinase (PI3K) pathway is showing great promise as anticancer drugs. This study compared SVEC mouse endothelial and PC-3 human prostate tumor cells in the response to verteporfin-mediated photodynamic therapy (PDT) and a pan-PI3K pathway inhibitor LY294002.MethodsVerteporfin cellular uptake and intracellular localization was determined by spectrofluorometry and confocal fluorescence microscopy, respectively, in the SVEC and PC-3 cells. Cytotoxicity induced by LY294002 and verteporfin-PDT was assessed by the MTS assay. Effects of treatments on cell survival and death signaling were examined by Western blot analysis.ResultsPC-3 cells had a higher cellular uptake of verteporfin than SVEC cells at 15Â min after incubation with verteporfin. Verteporfin was mainly localized in mitochondria in both SVEC and PC-3 cells. Verteporfin-PDT alone as well as PDT in combination with LY294002 induced more apoptosis and caused more reduction in cell viability in SVEC cells than in PC-3 cells. PC-3 cells exhibited a higher level of anti-apoptotic Bcl-2 family proteins than SVEC cells.ConclusionsSVEC cells were more responsive to verteporfin-PDT and PI3K pathway inhibitor LY294002 than PC-3 cells. Such differences in response were likely due to differences in Bcl-2 family protein level. These results support tumor vascular targeting by verteporfin-PDT and its therapeutic enhancement by PI3K pathway inhibition.
Journal: Photodiagnosis and Photodynamic Therapy - Volume 12, Issue 1, March 2015, Pages 19-26