TY - JOUR
T1 - Adenovirus-mediated human topoisomerase IIα gene transfer increases the sensitivity of etoposide-resistant human and mouse breast cancer cells
AU - Asano, Takeshi
AU - Kleinerman, Eugenie S.
AU - Zwelling, Leonard A.
AU - Zhou, Zhichao
AU - Fukunaga, Yoshitaka
N1 - Funding Information:
Supported by a Grant-in-Aid for Scientific Research C(2) from the Ministry of Education, Culture, Sports, Science, and Technology (10670147), a Young Investigator Award from the Nippon Medical School (1996), and the Uehara Research Fund (1996).
PY - 2005
Y1 - 2005
N2 - Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIα gene expression. Our previous studies have shown that transient transfection with a vector containing either Drosophila or human topoisomerase IIα gene into drug-resistant tumor cells enhanced their drug sensitivity. Furthermore, we constructed a recombinant adenovirus, Ad-hTopoIIα, containing the human topoisomerase IIα gene that was able to selectively increase etoposide sensitivity in drug-resistant tumor cells. We also examined Ad-hTopoIIα for therapeutic efficacy in vitro using additional etoposide-resistant cell lines, including a mouse breast cancer cell line and a human leukemia cell line. The etoposide-resistant mouse breast cancer cell line FvP, which is derived from FM3A, and etoposide-resistant human breast cancer cell line, MDA-VP, which derived from MDA-P cells showed increased sensitivity to etoposide as well as increased expression of human Topoisomerase IIα mRNA, but this was not seen in FM3A and MDA-P cells. On the other hand, the etoposide-resistant human leukemia cell line K562/MX2 and the parental cell line K562/P did not show enhanced sensitivity against etoposide or an increase in human Topoisomerase IIα mRNA. Using a recombinant adenovirus containing β-galactosidase gene (Ad-β-gal), K562 cells were not transducted by the recombinant adenovirus, while both etoposide-sensitive FM3A cells and etoposide resistant FvP cells were transducted by recombinant adenovirus. Ad-hTOP2α and etopside treatment showed reduced inoculated tumor weight in the mice. We concluded that a recombinant adenovirus containing the human Topoisomerase IIα gene might be a powerful tool for overcoming drug resistance in breast cancer cells, but not in leukemia cells.
AB - Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIα gene expression. Our previous studies have shown that transient transfection with a vector containing either Drosophila or human topoisomerase IIα gene into drug-resistant tumor cells enhanced their drug sensitivity. Furthermore, we constructed a recombinant adenovirus, Ad-hTopoIIα, containing the human topoisomerase IIα gene that was able to selectively increase etoposide sensitivity in drug-resistant tumor cells. We also examined Ad-hTopoIIα for therapeutic efficacy in vitro using additional etoposide-resistant cell lines, including a mouse breast cancer cell line and a human leukemia cell line. The etoposide-resistant mouse breast cancer cell line FvP, which is derived from FM3A, and etoposide-resistant human breast cancer cell line, MDA-VP, which derived from MDA-P cells showed increased sensitivity to etoposide as well as increased expression of human Topoisomerase IIα mRNA, but this was not seen in FM3A and MDA-P cells. On the other hand, the etoposide-resistant human leukemia cell line K562/MX2 and the parental cell line K562/P did not show enhanced sensitivity against etoposide or an increase in human Topoisomerase IIα mRNA. Using a recombinant adenovirus containing β-galactosidase gene (Ad-β-gal), K562 cells were not transducted by the recombinant adenovirus, while both etoposide-sensitive FM3A cells and etoposide resistant FvP cells were transducted by recombinant adenovirus. Ad-hTOP2α and etopside treatment showed reduced inoculated tumor weight in the mice. We concluded that a recombinant adenovirus containing the human Topoisomerase IIα gene might be a powerful tool for overcoming drug resistance in breast cancer cells, but not in leukemia cells.
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U2 - 10.1080/02841860510029653
DO - 10.1080/02841860510029653
M3 - Article
C2 - 16076696
AN - SCOPUS:21344470633
SN - 0284-186X
VL - 44
SP - 240
EP - 247
JO - Acta Oncologica
JF - Acta Oncologica
IS - 3
ER -