M. Ogihara et O. Yamaguchi, Potentiation of effects of anticancer agents by local electric pulses in murine bladder cancer, UROL RES, 28(6), 2000, pp. 391-397
Electrochemotherapy is a novel cancer treatment in which electric pulses (E
P) are used as a means of delivering anticancer agents to the cytoplasm of
cancer cells (electroporation). The present study evaluates whether electro
chemotherapy has in vitro and in vivo anticancer effects in murine bladder
cancer. Using mouse bladder tumor cells (MBT-2 cells), in vitro electrochem
otherapy was performed by applying EP to the cell suspension immediately af
ter the addition of anticancer agents. The cytotoxicity of adriamycin (ADM)
, bleomycin (BLM) and cis-diamminedichloroplatinum(II) (CDDP) was determine
d by measuring succinate dehydrogenase (SD) activity in both electroporated
and non-electroporated cells. In addition, intracellular concentrations of
these anticancer agents were also measured. In the in vivo study, tumor-be
aring C3H/He mice were treated with an intraperitoneal injection of antican
cer agents followed by a local delivery of EP at the tumor site. Then, tumo
r growth rate (TGR) was determined and compared to that in the sham-treated
control group, the EP-only group and the drug-only group. The in vitro stu
dy showed that, with electroporation, the cytotoxicity of BLM in electropor
ated cells was increased by as much as 95.7-fold compared to that of non-el
ectroporated MBT-2 cells; CDDP showed only an increase of 1.8-fold and ADM
showed no increase. After electroporation, the intracellular concentration
of BLM, CDDP and ADM showed an increase of 120-, 1.7- and 0.8-fold, respect
ively. In electrochemotherapy for in vivo growing tumors, the potentiation
of the antitumor effect was most prominent when combined with BLM, only sli
ghtly with CDDP, and totally absent with ADM. It is clear from in vitro and
in vivo studies that, in a murine bladder tumor, the anticancer effect of
BLM can be considerably potentiated by applying EP. Thus, BLM seems to be t
he most suitable anticancer agent for electrochemotherapy of bladder cancer
.