02 BOOK OF ABSTRACTS .indd

Electrogene therapy with p53 alone and in combination
with electrochemotherapy using cisplatin in treatment
of murine sarcomas
Alenka Gro{el, Maja ^ema`ar, Simona Kranjc, Suzana Mesojednik,
Gregor Tev`, Gregor Ser{a
Dept. of Experimental Oncology, Institute of Oncology, Zalo{ka 2,
SI-1000 Ljubljana, Slovenia
Electroporation is an established method for the delivery of molecules into
the cells. Biomedical application of electroporation in vivo is either delivery of
chemotherapeutic drugs - electrochemotherapy or DNA - electrically assisted gene
delivery or electrogene therapy. p53 plays crucial role in diverse cellular pathways
in response to DNA damage, one of them being apoptotic cell death. Cisplatin, a
commonly used chemotherapeutic agent, causes tumor cell death by producing
DNA damage and generating reactive oxygen intermediates. Our hypothesis was
that increased DNA damage due to increased cellular concentration of cisplatin by
electroporation e.g. electrochemotherapy would result in at least additive antitumor
effect in p53 electrogene therapy pre-treated tumors.
Aim of our study was to evaluate feasibility and therapeutic potential of electrogene
therapy with p53 alone or combined with electrochemotherapy using cisplatin in
two murine sarcomas with different p53 status.
In order to demonstrate feasibility and therapeutic potential murine subcutaneous
sarcomas (LPB and SA-1) were treated either with plasmid DNA, cisplatin or
electroporation and combinations of these treatments. Status of p53 in the tumors was
determined immunohistochemically, transfection efficacy by luciferase expression in
the tumors and antitumor effectiveness of the treatments by tumor growth delay and
determination of tumor free animals.
Antitumor effectiveness of three consecutive electrogene treatments with p53 was
dependent on the status of p53 being more effective in wild type LPB tumor than
in mutated SA-1 tumor. Pretreatment of tumors with electrogene therapy with p53
enhanced chemosensitivity of both tumor models treated by electrochemotherapy
with cisplatin. After only one treatment in LPB tumor model, tumor growth delay
was prolonged for 10 days in combined treatment group compared to electrogene
therapy with p53 or electrochemotherapy with cisplatin alone, whereas in SA-1
tumors this treatment combination resulted in 32% of cured animals.
In conclusion, results of our study show that electrogene therapy with p53 alone
or combined with electrochemotherapy is feasible and effective in treatment of
tumors. The combination of electrogene therapy and electrochemotherapy after
only one treatment resulted beside prolonged tumor growth delay also in tumor
free animals.
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