Changes of Morphological Characteristics and Metabolic Profile of Walker-256 Carcinosarcoma under the Impact of Exogenous Lactoferrin

Abstract

Numerous recent studies in experimental oncology have shown that the results of fundamental research at the current methodological level can serve as a sound basis for use in clinical practice. The aims of the present work were to assess the inhibitory effect of exogenous lactoferrin (LF) at doses of 1 and 10 mg/kg animal weight on the Walker-256 carcinosarcoma in vivo and the safety of its use, the distinctive features of changes in tumor tissue cytoarchitectonics, and the disturbances of energy metabolism and essential homeostasis at the tumor and organism level and to characterize the associative relationships and mechanisms that underlie these changes. Outbred rats were either administered exogenous LF nine times intraperitoneally at doses of 1 and 10 mg/kg body weight after Walker-256 carcinosarcoma grafting or served as control animals. The morphological analysis method was used for the evaluation of changes in tumor cytoarchitectonics under the influence of LF. The Hayashi cytogenetic method was used to assess the safety of exogenous LF. The content of essential elements was determined by atomic emission spectroscopy, and an atomic biochemical and enzyme-linked immunosorbent analyzer was used to evaluate the parameters of energy metabolism. Exogenous LF at the investigated doses inhibited the growth of Walker-256 carcinosarcoma, as is evident from the unidirectional changes in tumor architectonics: segregation of tumor cells, pycnosis, hyperchromatosis of the nuclei, necrobiosis and necrosis phenomena, and the resulting overall decrease in the tumor cell numbers; the effects on the blood vessels included dilation, wall thinning, and hemorrhage. The changes in the bioenergetic phenotype of tumor cells consisted in a decrease in glucose and lactate content. The homeostasis of essential elements, such as calcium, iron, and zinc, in the tumor tissue and blood plasma was disrupted by LF. The mechanisms that can underlie the specified effect of LF were inferred from the comparison of the abnormalities of tumor cytoarchitectonics, the vascular bed in particular, and the specific changes in the metabolic profiles of the tumors under the influence of exogenous LF.