Premium
Animal Model of Drug‐Resistant Tumor Progression
Author(s) -
MIRONOVA NADEZDA,
SHKLYAEVA OLGA,
ANDREEVA EKATERINA,
POPOVA NELLY,
KALEDIN VASILYI,
NIKOLIN VALERYI,
VLASSOV VALENTIN,
ZENKOVA MARINA
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.090
Subject(s) - cyclophosphamide , vinblastine , chemotherapy , cancer research , drug , drug resistance , phenotype , pharmacology , medicine , gene , biology , genetics
Experimental animal model of tumor progression based on mice lymphosarcoma (LS) and resistant lymphosarcoma (RLS) has been developed. LS tumor displays high sensitivity to cyclophosphamide, which is widely used in anticancer therapy. RLS tumor was derived from LS by passaging in mice receiving low concentration of cyclophosphamide (20 mg/kg) and display resistance to cyclophosphamide (up to dose 150 mg/kg).The primary cultures of LS and RLS tumors display different expression levels of the genes related to apoptosis and multiple drug‐resistant phenotype: in RLS tumor high levels of mdr1b and bcl‐2 genes and low level of p53 gene expression were found. A total of 10% of cells in RLS primary culture display multiple drug‐resistant phenotype and survive even at high dose of cytostatics. Cultivation of RLS primary culture in the presence of increasing vinblastine concentrations gives RLS 40 cell culture, which exhibits high levels of mdr1a/1b genes expression as compared to RLS and 20‐fold increase of resistance to cytostatics. Drug‐resistant RLS 40 cells were transplanted into CBA mice and sensitivity of the tumors to anticancer drugs was tested. RLS 40 tumors were resistant to a number of cytostatics used in anticancer therapy (cyclophosphamide, cysplatin, vinblastine, rubomycinum). Thus, RLS 40 tumor can be used as model, which corresponds to tumor status observed in patients after one or several courses of chemotherapy and can be useful for testing conventional therapy alone or together with newly developed gene‐targeted therapeutics.