02 BOOK OF ABSTRACTS .indd

Cytotoxicity and antitumour effectiveness of different
platinum (II) complexes alone or combined with
electroporation
Maja ^ema`ar 1 , @iva Pipan 2 , Sabina Grabner 3 , Nata{a Bukovec 3 ,
and Gregor Ser{a 1
1
Institute of Oncology, Zalo{ka 2, SI-1000 Ljubljana, Slovenia; 2 Biotechnical Faculty,
University of Ljubljana, Vecna pot 111, SI-1000 Ljubljana, Slovenia; 3 Faculty of Chemistry and
Chemical Technology, University of Ljubljana, A{ker~eva 5, SI-1000 Ljubljana, Slovenia
Cisplatin (CDDP), oxaliplatin (OXA) and carboplatin (CARBO) are platinum(II)
complexes that are already used in the clinical practice. Because of their side effects
to normal tissues and innate or acquired resistance new platinum (II) complexes are
being synthesized. The aim of our study was to determine in vitro cytotoxic activity
of two new platinum (II) complexes (3P-SK and PtAMP) in comparison with CDDP,
OXA and CARBO on four different human tumour cell lines (bladder carcinoma
T24, ovarian carcinoma IGROV1, ovarian resistant IGROV1/RDDP carcinoma and
mammary carcinoma MCF7 cells). Cells were plated into 96-well microtiter plates and
incubated with platinum complexes for 3 or 5 days at 37ºC in humidified atmosphere
containing 5% CO
p6
2
. Cytotoxicity of the complexes was determined by the colorimetric
MTT assay. The inhibitory concentration of the drug that reduced survival of cells to
50% (IC 50
) was determined for each cell line. In vivo we compared efficiency of CDDP
and one of the new platinum complex 3P-SK in MCA tumours induced in CBA mice.
Tumours were treated with different eqimolar doses of platinum compounds alone
or combined with application of electric pulses to the tumour (electrochemotherapy; 8 x 100 µs
pulses 1300 V/cm, 1 Hz). Tumour growth was followed by measuring three mutually
orthogonal tumour diameters (e 1
, e 2
, e 3
) with a vernier calliper. Doubling times of tumours
(DT) were determined for each individual tumour and tumour cures recorded.
The results of our study showed that CDDP and OXA were the most cytotoxic in all cells
used. One of the new platinum (II) complexes, 3P-SK, was more cytotoxic compared
to CARBO in all cells used, except in MCF7. The most sensitive cells to all complexes,
as determined by IC 50
, were human ovarian carcinoma IGROV1. IGROV1/RDDP cells
were the most resistant. Both OXA and CARBO were cross resistant with CDDP
(resistance level ∼20 fold) in CDDP resistant IGROV1/RDDP cells, while 3P-SK and
PtAMP circumvent the acquired CDDP resistance in the resistant subcloned cell line.
The levels of resistance were only 4-6 folds. Results in vivo showed that intratumoural
injection of 3P-SK alone or combined with electroporation (electrochemotherapy)
was effective treatment, inducing significantly prolonged growth delay and tumour
cures, but to the lesser extent compared to the CDDP based therapy.
In conclusion, our study showed that 3P-SK, a new platinum (II) complex is less
cytotoxic to human tumour cell lines that CDDP and OXA, but posses’ higher
cytotoxicity compared to CARBO. In experimental tumour model of mammary
carcinoma, treatment with 3P-SK alone or in combination with electroporation was
less effective compared to CDDP, but nevertheless resulted in tumour cures after
single application.
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