Remodulating effect of doxorubicin on the state of iron-containing proteins, and redox characteristics of tumor with allowance for its sensitivity to cytostatic agents

Abstract

The study was aimed at determining the changes of metal-containing proteins in blood serum and tumor tissue of animals with parental and doxorubicin-resistant strains of Walker-256 carcinosarcoma before and after the cytostatic administration. It has been shown that upon doxorubicin action the levels of total iron and transferrin in the tissues from the both groups of animals decreased while that of ferritine simultaneously increased with more pronounced pattern in the group of animals with resistant tumor strain. It has been shown that upon the action of doxorubicin in tumor tissue of animals with different sensitivity to the cytostatic there could be observed oppositely directed changes in the redox state of these cells that in turn determined the content of “ free iron” complexes, RO S generation and concentration of active forms of matrix metaloproteinase- 2 and matrix metaloproteinase-9, namely, the increase of these indexes in animals with parental strain and their decrease in animals with the resistant one. So, our study has demonstrated the remodulating effect of doxorubicin on the state of metal-containing proteins and redox characteristics of tumor dependent on its sensitivity to cytostatic, at the levels of the tumor and an organism. These data may serve as a criterion for the development of programs for the correction of malfunction of iron metabolism aimed at elevating tumor sensitivity to cytostatic agents.

Morphological Features of Doxorubicin-Resistant Walker 256 Carcinosarcoma and Response of Mast Cells

“…As was shown earlier, the formation of complete DOX resistance of Walker 56 carcinosarcoma in rats requires 12 passages in the setting of DOX treatment in vivo [15]. Four courses of chemotherapy result in partial DOX resistance with tumor growth inhibition by about 30%, while DOX treatment inhibited the growth of parental Walker-256 carcinosarcoma by about 65% [16]. These two time-points corresponding to partial (4 passages) and complete (12 passages) DOX resistance were selected for studying the morphological features of Walker 256 carcinosarcoma Morphologically, in DOX-resistant tumors we have found more structured patterns with formation of pseudo-follicular structures, slight outgrowth of the bundles of sarcomatous cells, and the activation of neoangiogenesis.…”

“…The rats were inoculated with original Walker 256 tumor cells or cells of DOX-resistant strain. Walker 256 carcinosarcoma with induced resistance to DOX was obtained as described earlier by serial transplantation of tumor cells in DOX-treated animals (12 in vivo passages in total) [15,16]. The tumors of the parental strain, the tumors after four in vivo passages in DOX setting (partial DOX resistance), and the tumors of the refractory phenotype (complete DOX resistance) were studied.…”