IMATINIB EFFECTIVELY INHIBITS HOMOLOGOUS RECOMBINATION AND SENSITIZES GASTROINTESTINAL STROMAL TUMOR CELLS
TO THE TOPOISOMERASE TYPE II INHIBITORS
S.V. Boichuk,1,* A.R. Galembikova,1 E.V. Martinova,2 B.R. Ramazanov,1 A. Duensing 3
1 Kazan State Medical University, Kazan, 420012, 2 Kazan (Volga Region) Federal University, Kazan, 420000,
and 3 University of Pittsburgh Cancer Institute, Pittsburgh, 15232, USA;
* e-mail: boichuksergei@mail.ru
Imatinib mesylate (IM) sensitizes gastrointestinal stromal tumor (GISTs) cell lines to the topoisomerase type
II inhibitors—doxorubicin and etoposide. IM substantially inhibited the cellular viability and induced apoptosis
of etoposide-treated GIST cells, whereas GIST cells showed lower etoposide cytotoxicity when treated
with etoposide alone. Similar effect was found in doxorubicin-treated GIST cells. These effects might be due
to the substantial down-regulation of Rad51 protein expression and inhibition of Rad51-mediated homologous
recombination DNA repair pathway. Of note, IM’s effect indicated above was observed in both imatinib-sensitive
(GIST882 and T-1) and resistant (GIST430) cell lines, and was not found in leiomyosarcoma SK-LMS-1
cell line.
Key words:
homologous recombination, Rad51, sensitization, apoptosis, imatinib, topoisomerase type II
inhibitors, gastrointestinal stromal tumors (GISTs)
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