TY - JOUR

T1 - КЛЕТКИ ГЛИОБЛАСТОМ ЧЕЛОВЕКА ЛИНИЙ Т2 И Т98G, РЕЗИСТЕНТНЫЕ К ДЕЙСТВИЮ ТЕМОЗОЛОМИДА

AU - Pinevich, A. A.

AU - Bode, I. I.

AU - Vartanyan, N. L.

AU - Kartashev, A. V.

AU - Samoilovich, M. P.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - The generation of tumor cells resistant to chemo- and radiation therapy is one of the unresolved problems of oncology. The study of the conditions and mechanisms of temozolomide (first-line drug in glioblastoma therapy) resistance formation is carried out on cultured cell lines. Considering the heterogeneity of glioblastomas, it is important to study the responses of different cell lines to temozolomide. The aim of this work was to obtain and characterize temozolomide-resistant T2 and T98G cell lines. The source of temozolomide was the drug Temodal® in lyophilized form for preparation of an infusion solution. T98G cells are known to be highly resistant to temozolomide; the response of T2 cells to the drug has not been studied yet. A single exposure to 1 mM temozolomide resulted in changes in T2 cell populations composition - an increase of the proportion of giant mononuclear cells and cells with fragmented nuclei. As a result, the number of cells in G0/G1 cell cycle phases decreased, while the number of polyploid cells increased by four times. The cells that reactivated proliferation and were exposed to 2 mM temozolomide for the second and third times differed morphologically and in proliferation activity from the cells that underwent a single treatment, and approximated to the intact cells in many respects. After a single incubation with 2 mM temozolomide T2 cells recovered 90% monolayer in 48 days, after the second treatment - in 13 days, and after the third exposure - in 2 days only. Temozolomide resistance formation by T2 cells was not accompanied by changes in the initially high levels of multiple drug resistance genes ABCC1, ABCG2, and ABCB1 activities, as well as MGMT gene activity. The formation of temozolomide resistance in T2 glioblastoma cell culture is most likely due to the action of other mechanisms. Consequently, T2 cell line can provide a source of temozolomide-resistant cells and be used as a model of recurrent glioblastoma. T98G cells, as expected, showed an extremely high level of resistance to temozolomide. The drug at doses lower than 5 mM had no prominent effect on these cells.

AB - The generation of tumor cells resistant to chemo- and radiation therapy is one of the unresolved problems of oncology. The study of the conditions and mechanisms of temozolomide (first-line drug in glioblastoma therapy) resistance formation is carried out on cultured cell lines. Considering the heterogeneity of glioblastomas, it is important to study the responses of different cell lines to temozolomide. The aim of this work was to obtain and characterize temozolomide-resistant T2 and T98G cell lines. The source of temozolomide was the drug Temodal® in lyophilized form for preparation of an infusion solution. T98G cells are known to be highly resistant to temozolomide; the response of T2 cells to the drug has not been studied yet. A single exposure to 1 mM temozolomide resulted in changes in T2 cell populations composition - an increase of the proportion of giant mononuclear cells and cells with fragmented nuclei. As a result, the number of cells in G0/G1 cell cycle phases decreased, while the number of polyploid cells increased by four times. The cells that reactivated proliferation and were exposed to 2 mM temozolomide for the second and third times differed morphologically and in proliferation activity from the cells that underwent a single treatment, and approximated to the intact cells in many respects. After a single incubation with 2 mM temozolomide T2 cells recovered 90% monolayer in 48 days, after the second treatment - in 13 days, and after the third exposure - in 2 days only. Temozolomide resistance formation by T2 cells was not accompanied by changes in the initially high levels of multiple drug resistance genes ABCC1, ABCG2, and ABCB1 activities, as well as MGMT gene activity. The formation of temozolomide resistance in T2 glioblastoma cell culture is most likely due to the action of other mechanisms. Consequently, T2 cell line can provide a source of temozolomide-resistant cells and be used as a model of recurrent glioblastoma. T98G cells, as expected, showed an extremely high level of resistance to temozolomide. The drug at doses lower than 5 mM had no prominent effect on these cells.

KW - ABCB1

KW - ABCC1

KW - ABCG2

KW - glioblastoma

KW - MGMT

KW - resistant cells

KW - T2

KW - T98G

KW - Temodal®

KW - temozolomide

UR - http://www.scopus.com/inward/record.url?scp=85135822341&partnerID=8YFLogxK

U2 - 10.31857/S0041377122020043

DO - 10.31857/S0041377122020043

M3 - статья

AN - SCOPUS:85135822341

VL - 64

SP - 126

EP - 140

JO - Цитология

JF - Цитология

SN - 0041-3771

IS - 2

ER -