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

  • SIMONA KRANJC Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana
  • Maja Cemazar Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana & University of Primorska, Faculty of Health Sciences, Polje 24, SI-4000 Izola
  • Gregor Sersa Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana & Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana
  • Janez Scancar Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana
  • Sabina Grabner Faculty of Chemistry and Chemical Technology, University of Ljubljana, Vecna pot 113, SI-1000 Ljubljana

Abstract

Background. 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 trans-[PtCl2(3-Hmpy)2] (3-Hmpy = 3-hydroxymethylpyridine) (compound 2) showed a considerable cytotoxic and antitumour efficiency. To improve compound 2 cytotoxicity in vitro and antitumour efficiency in vivo, electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy).

Materials and methods. In vitro, 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 2 or cisplatin electrochemotherapy. In vivo, the antitumour effectiveness of electrochemotherapy with compound 2 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.

Results. In vitro, cell survival after treatment with compound 2 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 2 cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells. In vivo, the growth delay of subcutaneous tumours after treatment with compound 2 electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound 2 electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound 2 induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound 2 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.

Conclusion. The obtained results in vitro and in vivo suggest compound 2 as a potential antitumour agent in electrochemotherapy.

Keywords: platinum analogue, cisplatin, 3-Hmpy, electroporation, electrochemotherapy, mouse sarcoma

Author Biographies

SIMONA KRANJC, Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana

Department of Experimental Oncology

Research assistant, PhD

Maja Cemazar, Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana & University of Primorska, Faculty of Health Sciences, Polje 24, SI-4000 Izola

Department of Experimental Oncology

Deputy Head, Prof., PhD

Gregor Sersa, Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana & Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana

Department of Experimental Oncology

Head of the Department, Prof., PhD

Janez Scancar, Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana
Senior Researcher, Head of the Group for Inorganic Environmental Analytical Chemistry, PhD
Sabina Grabner, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Vecna pot 113, SI-1000 Ljubljana
Chair of Inorganic Chemistry, Assistant, PhD
Published
2017-09-10
How to Cite
KRANJC, S., Cemazar, M., Sersa, G., Scancar, J., & Grabner, S. (2017). In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]. Radiology and Oncology, 51(3). Retrieved from https://radioloncol.com/index.php/ro/article/view/2871
Section
Experimental oncology