Platinum-based antitumour agents play critical role in the treatment of ovarian carcinomas. The initial response rate is high but one-third originally responsive patients develop chemoresistance during the course of their treatment. This gives an incentive to seek other Pt complexes with lesser side effects and strong disease-oriented action. Such requirements seem to be fulfilled by the hydroxydicarboxylatoplatinum complexes which are the object of our study: ethylenediamine(L-malato)platinum(II), (Pt-en-L-mal), and bis(1-ethylimidazole)(L-malato)platinum(II), (Pt-etim-L-mal).

The present study was undertaken to examine the influence of cisplatin and new cytotoxic platinum complexes on expression of multi-drug resistant proteins (P-gp, MRP, LRP), apoptosis related proteins (Bax, p53, Bcl-2) and mismatch repair gene product (hMLH1) in OvBH-1 cell line.

The expressions of all proteins were assessed and compared on OvBH-1 cells, before and after treatment with drugs, by immunohistochemical staining using monoclonal antibodies. The results of immunohistochemical study show the big differences in the action of platinum species. In particular, only exposure to cisplatin increased expression of P-gp, MRP and LRP whereas the expression of apoptosis related protein, Bcl-2, was strongly stimulated only by Pt-etim-L-mal. However, the nuclear accumulation of p53 was found in a similar percentage of all treated and untreated cells. Finally, the above facts together with observation of big and different influences of platinum species on hMLH1 expression may indicate that, in OvBH-1 cells, some of examined drugs activate the DNA mismatch repair mechanism on the way independent on p53 expression. The presented results will be confronted with the settlements from the study of biological properties of malatoplatinum complexes on cellular and DNA levels.

Using AFM technique we studied and imagined the influence of platinum drugs on the surface of OvBH-1 cells. It was found that the surface relief of ovarian cell membrane in nanometer scale differs from the membrane of platinum-treated cells. We also could notice the differences between action of cisplatin and carboplatin on the cell surface which might dependent on P53 status in OvBH-1 cell line. The differences seem to be a result of various changes caused by these drugs in membrane protein structure.

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