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

Abstract

Background: The mechanisms of drug resistance of cancer have not been yet elucidated in details. Recently, the role of mast cells (MCs) in the development of drug resistance has been brought in the limelight. The aim of the study was to examine the morphological features of doxorubicin (DOX)-resistant Walker 256 carcinosarcoma and to assess the response of MCs and histamine content in these cells in relation to the development of resistance to DOX as well as in DOX-resistant tumors. Materials and Methods: The DOX resistance was induced by serial passages of Walker 256 carcinosarcoma in rats in the setting of DOX treatment in vivo. MCs in tumors were detected in the sections by staining with Toluidine Blue O. Histamine content in MCs stained with solution of Water Blue-Orcein was assessed by Astaldi semiquantitative method taking into account different staining intensity. Results: Formation of DOX resistance in the course of serial passages of Walker 256 carcinosarcoma was accompanied by the increase in the number of MCs in tumors and histamine content. Nevertheless, in tumors with phenotype of complete DOX resistance the number of histamine-containing MCs decreased to the same level as in tumors of the original strain that are DOX-sensitive. Conclusion: MCs are involved in formation of DOX resistance in Walker 256 carcinosarcoma.

Effects induced by a 50 Hz electromagnetic field and doxorubicin on Walker-256 carcinosarcoma growth and hepatic redox state in rats

“…DOX + EMF treatment caused both necrosis and apoptosis of tumor cells. The development of fibrotic tissue accompanied tumor adaptation to DOX chemotherapy (Boroday and Chekhun 2018) and tissue replacement (Lushnikova et al 2011). These results are consistent with previous investigations, which showed that the mechanism of tumor and liver cell death under the influence of EMF was apoptosis (Alves de Souza et al 2017;Ghodbane et al 2015;Lai 2019).…”

“…H&E stained tissue slides were examined under a light microscope (Olympus BX-41, Olympus Europe GmbH, Japan) according to (Thoolen et al 2010). The assessment of changes in tumor and liver tissues was performed using the histological criteria defined by (Boroday and Chekhun 2018).…”