Total proteolytic activity and levels of the main proteinase inhibitors in blood plasma of mice bearing Lewis lung carcinoma upon development of resistance to cisplatin.
The aim of the study was to evaluate the total proteolytic activity (TPA) and the content of alpha-1-proteinase inhibitor (alpha1PI) and alpha-2-macroblobulin (alpha2M) in the blood plasma of mice with Lewis lung carcinoma (LLC) upon the development of resistance to cisplatin.


METHODS
Experimental LLC model with different sensitivity to cisplatin was obtained by sequential subcutaneous transplantation of LLC cells from cisplatin-treated animals. TPA, alpha1PI and alpha2M levels were evaluated by standard biochemical methods.


RESULTS
It has been shown that the development of LLC resistance to cisplatin is accompanied by the increase of TPA activity and the level of the main proteinase inhibitor - alpha1PI. Despite the high level of alpha1PI in the resistant variant of LLC compared to parental tumor, the increase of TPA/alpha1PI ratio indicated the deficiency of that inhibitor in the blood of mice bearing cisplatin-resistant tumors, that promotes metastasis. The growth of both resistant to cisplatin LLC and sensitive variant was accompanied with the reduction of the alpha2M concentration.


CONCLUSIONS
Upon the development of resistance to cisplatin in vivo the shift in the balance between proteinases and their inhibitors toward activation of TPA simultaneously with the increased metastasis is taking place.
Chekhun
V F
VF
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Kovtonyuk
O V
OV
Todor
I N
IN
Kulik
G I
GI
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000097:blood* / Q000188:drug therapy; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D008297:Male; D051379:Mice; D011480:Protease Inhibitors / Q000097:blood; D012697:Serine Endopeptidases / Q000097:blood
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; D002945:Cisplatin