Photodynamic therapy combined with a cysteine proteinase inhibitor synergistically decrease VEGF production and promote tumour necrosis in a rat mammary carcinoma

光动力疗法与半胱氨酸蛋白酶抑制剂联合使用可协同减少大鼠乳腺癌中的 VEGF 产生并促进肿瘤坏死

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作者:B Zsebik, K Symonowicz, Y Saleh, P Ziolkowski, A Bronowicz, G Vereb

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.

Methods

Intraperitoneally injected single doses of chlorine e6 or HpD as photosensitizers were excited at 630 nm (90 J/cm(2)). CPI (500 micro g 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.

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