ID 110665
Author
Yano, Seiji Third Department of Internal Medicine, The University of Tokushima School of Medicine
Yanagawa, Hiroaki Third Department of Internal Medicine, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Hanibuchi, Masaki Third Department of Internal Medicine, The University of Tokushima School of Medicine KAKEN Search Researchers
Pai, Kalpana Third Department of Internal Medicine, The University of Tokushima School of Medicine
Nishioka, Yasuhiko Third Department of Internal Medicine, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tsuruo, Takashi Institute of Molecular and Cellular Biosciences, The University of Tokyo
Sone, Saburo Third Department of Internal Medicine, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
multidrug resistance
P-glycoprotein
ganglioside GM2
ADCC
cyclosporin A
Content Type
Journal Article
Description
A P-glycoprotein (P-gp) inhibitor, cyclosporin A (CsA) was found to enhance the susceptibility of multidrug resistant (MDR) cancer cells to anti-P-gp antibody-dependent cellular cytolysis (ADCC) by monocytes, but the exact mechanism is unknown. In this study, we examined whether CsA enhanced the susceptibility of MDR cells through its inhibitory effect of P-gp function by using anti-ganglioside GM2 (GM2) monoclonal antibody (Ab), KM966, instead of anti-P-gp Ab, MRK16. Monocyte-ADCC induced by both KM966 and MRK16 against P-gp positive human MDR ovarian cancer cells was significantly augmented by addition of CsA. KM966, but not MRK16, induced monocyte-ADCC against P-gp negative human ovarian cancer cells and CsA enhanced this ADCC activity, indicating that suppressive effect of P-gp function by CsA was not essential to the enhancement of ADCC. Moreover, pretreatment of tumor cells with CsA augmented their susceptibility to monocyte-ADCC irrespective of P-gp expression. Interestingly, KM966 or MRK16 induced monocyte-ADCC against various human lung cancer cells expressing either GM2 or P-gp, but CsA did not affect these ADCC. These findings suggest that CsA may enhance the susceptibility to the monocyte-ADCC of ovarian cancer cells, but not of lung cancer cells, irrespective of its suppressive effect of P-gp function.
Journal Title
The journal of medical investigation : JMI
ISSN
13431420
NCID
AA11166929
Volume
44
Issue
3-4
Start Page
185
End Page
191
Sort Key
185
Published Date
1998
EDB ID
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Medical Sciences