Open AccessPhotodynamic therapy combined with a cysteine proteinase inhibitor synergistically decrease VEGF production and promote tumour necrosis in a rat mammary carcinoma
Author(s) -
Zsebik B.,
Symonowicz K.,
Saleh Y.,
Ziolkowski P.,
Bronowicz A.,
Vereb G.
Publication year - 2007
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2007.00420.x
Subject(s) - necrosis , photodynamic therapy , cathepsin b , haematoxylin , pathology , carcinoma , proteases , vascular endothelial growth factor , medicine , staining , cancer research , andrology , biology , chemistry , vegf receptors , enzyme , biochemistry , organic chemistry
. Objectives : Photodynamic therapy (PDT) and inhibition of cathepsin B proteases by cystatin (cysteine proteinase inhibitor, CPI) are potential new tumour treatment modalities. We have investigated the efficacy of PDT and CPI alone and in combination on a solid mammary carcinoma transplanted into Wistar rats. Materials and Methods : Intraperitoneally injected single doses of chlorine e6 or HpD as photosensitizers were excited at 630 nm (90 J/cm 2 ). CPI (500 µg per animal) was injected around the tumour daily during the 8‐day treatment. Inoculation of tumour was either on day 1 of the protocol, or 8 days before. On day 8, tumour size was measured, tumour necrosis and vascularization were determined based on haematoxylin and eosin (H&E)‐stained sections and serum vascular endothelial growth factor (VEGF) levels measured using an enzyme‐linked immunosorbent assay kit. Results : No differences (two‐way anova ) were found for treatments started with various time lags. At doses where CPI or PDT alone had no or negligible effect, their combination caused a marked ( P < 0.001) decrease in serum VEGF, paralleled by a significant decrease in tumour size and number of capillary vessels, and a significant increase in necrosis (up to 80% of the tumour tissue). Conclusions : The combination of PDT and CPI could be a useful approach in tumour therapy as the two agents appear to be synergistic and probably decrease VEGF production by the tumour tissue.