Tumor blood flow modifying effect of electrochemotherapy with bleomycin

Electrochemotherapy combines administration of the chemotherapeutic drug, followed by application of electric pulses in order to increase drug delivery into the cells. The aim of this study was to determine the tumor blood flow modifying effect of electrochemotherapy with bleomycin and correlate it with its antitumor effectiveness and extent of tumor necrosis.

Electrochemotherapy of SA-1 subcutaneous tumors in A/J mice was performed by application of electric pulses to the tumors, following administration of bleomycin, and antitumor effectiveness determined by tumor growth delay and tumor cures as well as extent of tumor necrosis. Tumor blood modifying effect of therapy was evaluated by Patent blue staining technique and 86RbCl extraction technique.

A good correlation of the two methods evaluating tumor blood flow, Patent blue staining and the established 86RbCl extraction technique was found (r = 0.944). Electrochemotherapy resulted in complete and permanent shut down of tumor blood flow within 12 hours, which lasted for at least 5 days. The results on tumor blood flow reduction correlated well with the good antitumor effectiveness of electrochemotherapy and with the extent of the necrosis in the tumors.

The results indicate that Patent blue staining technique is a simple and reliable method for estimation of tumor blood flow and that antitumor effectiveness of electrochemotherapy with bleomycin could be partly attributed to its tumor blood modifying and anti-vascular effect.