The role of expression of the components of proteome in the formation of molecular profile of human ovarian carcinoma A2780 cells sensitive and resistant to cisplatin.
OBJECTIVE
To study the expression of proteins that characterize drug resistance, proliferation and apoptosis of human ovarian carcinoma cells.


METHODS
The study was carried out on human ovarian carcinoma A2780 cells and on the A2780/DDP8 subline resistant to cisplatin. Expression of the surface and intracellular antigens (p53, Bcl-2, CD95, antigen of proliferating cells, metallothioneins, drug resistance proteins (P-glycoprotein (P-gp), glutathione-S-transferase), molecules of adhesion (E-cadherin, alpha- and beta-catenins) was studied by immunocytochemical method.


RESULTS
It has been shown that the formation of the resistance to cisplatin in A2780/DDP8 cells is accompanied by the increase of expression of glutathione-S-transferase and Bcl-2, by the decrease of expression of CD95-antigene and proliferation potential of the cells, by appearance of EGF receptors and elevation of expression level of E-cadherin, alpha- and beta-catenins, proving the enhancement of adhesive properties of tumor cells.


CONCLUSIONS
Antiapoptotic program seems to be the leading mechanism of the development of the resistance to cisplatin in A2780/DDP8 cells and is realized via high expression of Bcl-2. During the development of drug resistance of A2780/DDP cells, the program of glutathione detoxification is functionally replacing the decrease of the content of metallothioneins.
Chekhun
V F
VF
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, Kyiv 03022, Ukraine.
Lukyanova
N Yu
NY
Urchenko
O V
OV
Kulik
G I
GI
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D005982:Glutathione Transferase; D002945:Cisplatin