ID 110741
Author
Matsumoto, Yoshihito Department of Neurological Surgery, Kagawa University School of Medicine
Miyake, Keisuke Department of Neurological Surgery, Kagawa University School of Medicine
Kunishio, Katsuzou Department of Neurological Surgery, Kagawa University School of Medicine
Tamiya, Takashi Department of Neurological Surgery, Kagawa University School of Medicine
Nagao, Seigo Department of Neurological Surgery, Kagawa University School of Medicine
Keywords
antisense
multidrug resistance
gene therapy
MRP
glioma
Content Type
Journal Article
Description
The tumor cells’ acquisition of resistance to multiple drugs due to overexpression of the multidrug resistance protein(MRP) 1gene is one of major obstacles in cancer chemotherapy. We have attempted to reverse the multidrug resistance (MDR) phenotype by treating etoposide resistant glioma cell lines (T98G-VP and Gli36-VP) with MRP1 antisense oligonucleotides. 20-mer phosphorothioate oligodeoxynucleotide (0.3μM), complementary to the coding region in the MRP cDNA sequence, could significantly inhibit the growth of multidrug resistant cell lines, T98G-VP and Gli36-VP, cultured in etoposide containing medium. No such effect was observed for the parental T98G and Gli36 cell lines. Further investigations by the reverse transcription-polymerase chain reaction and immunoblotting revealed that antisense oligomer could result in a reduction in the level of MRP1 mRNA, probably through hindering MRP1 gene transcription. This study demonstrates that the antisense oligonucleotides can increase the sensitivity of the tumor cells to the anticancer drug by decreasing the expression of the MRP gene. This strategy may be applicable to cure cancer patients with MRP mediated MDR phenotype.
Journal Title
The journal of medical investigation : JMI
ISSN
13431420
NCID
AA11166929
Volume
51
Issue
3-4
Start Page
194
End Page
201
Sort Key
194
Published Date
2004-08
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher