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. 1999 Mar;79(9-10):1386–1391. doi: 10.1038/sj.bjc.6690222

Increased platinum accumulation in SA-1 tumour cells after in vivo electrochemotherapy with cisplatin

M C̆emaz̆ar 1, D Miklavc̆ic̆ 2, J S̆c̆anc̆ar 3, V Dolz̆an 4, R Golouh 1, G Sers̆a 1
PMCID: PMC2374264  PMID: 10188880

Abstract

Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability caused by electroporation that enables cisplatin binding to DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on SA-1 tumours treated with electric pulses 3 min after intravenous injection of cisplatin (4 mg kg−1). Anti-tumour effectiveness was correlated with platinum accumulation in tumours and the amount of platinum bound to DNA, as determined by atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell kill was increased by a factor of 20 compared with treatment with cisplatin only, as determined from tumour growth curves. The amount of platinum bound to DNA and platinum content in the tumours treated by electrochemotherapy was approximately two times higher than in cisplatin-treated tumours. Based on our results, we conclude that in vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin increased delivery into the cells. In addition, besides electroporation, immune system and tumour blood flow changes could be involved in the observed anti-tumour effectiveness of electrochemotherapy. © 1999 Cancer Research Campaign

Keywords: cisplatin, platinum, electroporation, electrochemotherapy, electrothermal atomic absorption spectrometry

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Selected References

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  1. Belehradek J., Jr, Orlowski S., Ramirez L. H., Pron G., Poddevin B., Mir L. M. Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin. Biochim Biophys Acta. 1994 Feb 23;1190(1):155–163. doi: 10.1016/0005-2736(94)90045-0. [DOI] [PubMed] [Google Scholar]
  2. Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J Biol Chem. 1994 Jan 14;269(2):787–790. [PubMed] [Google Scholar]
  3. Gately D. P., Howell S. B. Cellular accumulation of the anticancer agent cisplatin: a review. Br J Cancer. 1993 Jun;67(6):1171–1176. doi: 10.1038/bjc.1993.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Jekunen A. P., Shalinsky D. R., Hom D. K., Albright K. D., Heath D., Howell S. B. Modulation of cisplatin cytotoxicity by permeabilization of the plasma membrane by digitonin in vitro. Biochem Pharmacol. 1993 May 25;45(10):2079–2085. doi: 10.1016/0006-2952(93)90019-s. [DOI] [PubMed] [Google Scholar]
  5. Marverti G., Andrews P. A., Piccinini G., Ghiaroni S., Barbieri D., Moruzzi M. S. Modulation of cis-diamminedichloroplatinum (II) accumulation and cytotoxicity by spermine in sensitive and resistant human ovarian carcinoma cells. Eur J Cancer. 1997 Apr;33(4):669–675. doi: 10.1016/s0959-8049(96)00507-2. [DOI] [PubMed] [Google Scholar]
  6. Melvik J. E., Pettersen E. O., Gordon P. B., Seglen P. O. Increase in cis-dichlorodiammineplatinum (II) cytotoxicity upon reversible electropermeabilization of the plasma membrane in cultured human NHIK 3025 cells. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1523–1530. doi: 10.1016/0277-5379(86)90090-8. [DOI] [PubMed] [Google Scholar]
  7. Milacic R., Cemazar M., Sersa G. Determination of platinum in tumour tissues after cisplatin therapy by electrothermal atomic absorption spectrometry. J Pharm Biomed Anal. 1997 Oct;16(2):343–348. doi: 10.1016/s0731-7085(97)00045-9. [DOI] [PubMed] [Google Scholar]
  8. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mir L. M., Glass L. F., Sersa G., Teissié J., Domenge C., Miklavcic D., Jaroszeski M. J., Orlowski S., Reintgen D. S., Rudolf Z. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer. 1998 Jun;77(12):2336–2342. doi: 10.1038/bjc.1998.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mir L. M., Orlowski S., Belehradek J., Jr, Paoletti C. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer. 1991;27(1):68–72. doi: 10.1016/0277-5379(91)90064-k. [DOI] [PubMed] [Google Scholar]
  11. Mir L. M., Tounekti O., Orlowski S. Bleomycin: revival of an old drug. Gen Pharmacol. 1996 Jul;27(5):745–748. doi: 10.1016/0306-3623(95)02101-9. [DOI] [PubMed] [Google Scholar]
  12. Okino M., Mohri H. Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res. 1987 Dec;78(12):1319–1321. [PubMed] [Google Scholar]
  13. Orlowski S., Mir L. M. Cell electropermeabilization: a new tool for biochemical and pharmacological studies. Biochim Biophys Acta. 1993 Jun 8;1154(1):51–63. doi: 10.1016/0304-4157(93)90016-h. [DOI] [PubMed] [Google Scholar]
  14. Poddevin B., Orlowski S., Belehradek J., Jr, Mir L. M. Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture. Biochem Pharmacol. 1991 Dec 11;42 (Suppl):S67–S75. doi: 10.1016/0006-2952(91)90394-k. [DOI] [PubMed] [Google Scholar]
  15. Sersa G., Cemazar M., Miklavcic D. Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res. 1995 Aug 1;55(15):3450–3455. [PubMed] [Google Scholar]
  16. Sersa G., Stabuc B., Cemazar M., Jancar B., Miklavcic D., Rudolf Z. Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients. Eur J Cancer. 1998 Jul;34(8):1213–1218. doi: 10.1016/s0959-8049(98)00025-2. [DOI] [PubMed] [Google Scholar]

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