Cytotoxicity of bioreductive drug tirapazamine is increased by application of electric pulses in SA-1 tumours in mice.

摘要

The application of electrical pulses (electroporation) is a local tumour treatment resulting in the facilitated accumulation of non-permeant chemotherapeutic drugs (electrochemotherapy), as well as in the transient reduction of tumour blood flow. The aim of our study was to determine whether the application of electric pulses to the tumour increased the antitumour effectiveness of the bioreductive drug tirapazamine (TPZ). The survival of SA-1 fibrosarcoma cells was 150-fold lower after the exposure of cells for 1 h to TPZ under anoxic compared with normoxic conditions. The exposure of cells to electric pulses did not increase the cytotoxicity of TPZ. However, the in vivo treatment of subcutaneous tumours with a combination of TPZ (i.p. 25 mg/kg) injected 20 min before the application of electrical pulses significantly enhanced tumour response. Treatment with TPZ and electric pulses, repeated three times at 24-hour intervals resulted in tumour growth delay of 7.2 days. The results of our study showed that the observed antitumour effectiveness is unlikely to be due to increased cellular accumulation of TPZ by application of electric pulses, as indicated from in vitro experiments. The effect is more likely to be attributed to increased tumour hypoxia as a consequence of reduced tumour blood flow induced by application of electric pulses.