Cemazar M, Parkins C S, Holder A L, Kranjc S, Chaplin D J, Sersa G
Department of Tumor Biology, Institute of Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia.
Anticancer Res. 2001 Mar-Apr;21(2A):1151-6.
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.
电脉冲（电穿孔）的应用是一种局部肿瘤治疗方法，可促进非渗透性化疗药物的积聚（电化学疗法），同时使肿瘤血流短暂减少。我们研究的目的是确定对肿瘤施加电脉冲是否会提高生物还原药物替拉扎明（TPZ）的抗肿瘤效果。与常氧条件相比，SA - 1纤维肉瘤细胞在缺氧条件下暴露于TPZ 1小时后的存活率降低了150倍。细胞暴露于电脉冲并未增加TPZ的细胞毒性。然而，在施加电脉冲前20分钟腹腔注射TPZ（25 mg/kg）联合电脉冲对皮下肿瘤进行体内治疗，显著增强了肿瘤反应。以24小时间隔重复三次TPZ和电脉冲治疗，导致肿瘤生长延迟7.2天。我们的研究结果表明，如体外实验所示，观察到的抗肿瘤效果不太可能是由于施加电脉冲增加了TPZ在细胞内的积聚。这种效果更可能归因于电脉冲引起的肿瘤血流减少导致肿瘤缺氧增加。
