In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]

• Published in: Radiology and oncology 2017-09, Vol.51 (3), p.295-306
• Main Authors: Kranjc, Simona, Cemazar, Maja, Sersa, Gregor, Scancar, Janez, Grabner, Sabina
• Format: Article
• Language: English
• Subjects: 3-Hmpy; Anticancer properties; Antitumor activity; Biocompatibility; Body weight; Cancer therapies; Cell survival; Chemotherapy; Cisplatin; Cures; Cytotoxicity; Delay; Deoxyribonucleic acid; DNA; Drug delivery; Drug delivery systems; Effectiveness; electrochemotherapy; Electroporation; Evaluation; In vitro methods and tests; Inductively coupled plasma mass spectrometry; Mass spectrometry; Mass spectroscopy; Membrane permeability; mouse sarcoma; Permeability; Platinum; platinum analogue; Platinum compounds; Sarcoma; Sensitivity; Side effects; Survival; Toxicity; Tumors
• ISSN: 1318-2099; 1581-3207; 1581-3207; 0485-893X
• DOI: 10.1515/raon-2017-0034

Cisplatin is used in cancer therapy, but its side effects and acquired resistance to cisplatin have led to the synthesis and evaluation of new platinum compounds. Recently, the synthesized platinum compound -[PtCl (3-Hmpy) ] (3-Hmpy = 3-hydroxymethylpyridine) (compound ) showed a considerable cytotoxic and antitumour effectiveness. To improve compound cytotoxicity and antitumour effectiveness , electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy). , survival of sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive) was determined using a clonogenic assay after treatment with compound or cisplatin electrochemotherapy. , the antitumour effectiveness of electrochemotherapy with compound or cisplatin was evaluated using a tumour growth delay assay. In addition, platinum in the serum, tumours and platinum bound to the DNA in the cells were performed using inductively coupled plasma mass spectrometry. , cell survival after treatment with compound electrochemotherapy was significantly decreased in all tested sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive). However, this effect was less pronounced compared to cisplatin. Interestingly, the enhancement factor (5-fold) of compound cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells. , the growth delay of subcutaneous tumours after treatment with compound electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound or cisplatin electrochemotherapy were approximately 2-fold higher compared to the drug treatment only, and the same increase of platinum bound to DNA was observed. The obtained results and suggest compound as a potential antitumour agent in electrochemotherapy.