Cytotoxicity of different platinum (II) analogues to human tumour cell lines in vitro and murine tumour in vivo alone or combined with electroporation.
BACKGROUND
The in vitro cytotoxic activity of two new platinum(II) complexes (3P-SK and PtAMP) in comparison with cisplatin (CDDP), oxaliplatin (OXA) and carboplatin (CARBO) was determined in four different human tumour cell lines. The in vivo efficiencies of CDDP and 3P-SK in MCA mammary carcinoma tumours induced in CBA mice were compared.


METHODS
The in vitro cytotoxicity of the platinum (II) complexes was determined by the colorimetric MTT assay. The tumours were treated with different doses of platinum compounds, alone or combined with the local application of electric pulses to the tumour (electrochemotherapy). The antitumour effectiveness was determined by tumour growth inhibition.


RESULTS
CDDP and OXA were the most cytotoxic in all cells tested. 3P-SK was more cytotoxic when compared to CARBO in all cells tested, except in MCF7. Intratumoral injection of 3P-SK alone or combined with electroporation (electrochemotherapy) induced significant tumour growth delay and tumour cure.


CONCLUSIONS
3P-SK was found to be less cytotoxic to human tumour cell lines than CDDP and OXA, but displayed a higher cytotoxicity compared to CARBO. In the 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 growth inhibition after a single application.
Cemazar
Maja
M
Department of Experimental Oncology, Institute of Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia. mcemazar@onko-i.si
Pipan
Ziva
Z
Grabner
Sabina
S
Bukovec
Natasa
N
Sersa
Gregor
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D018274:Electroporation / Q000379:methods; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008808:Mice, Inbred CBA; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin