当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF CANCER期刊下所有文献 > Differential intracellular processing of the anthracycline drug ME2303 in doxorubicin-sensitive (A2780) and -resistant (A2780AD) human ovarian cancer cells as studied with confocal laser scanning microscopy and image analysis.

Differential intracellular processing of the anthracycline drug ME2303 in doxorubicin-sensitive (A2780) and -resistant (A2780AD) human ovarian cancer cells as studied with confocal laser scanning microscopy and image analysis.

Abstract：

:Laser scanning confocal microscopy has been used to follow the uptake and efflux of the 2-fluoroglycoside of doxorubicin, ME2303, in live cultures of the human ovarian cancer cell line A2780 and its doxorubicin-resistant variant A2780AD. Our methods combine confocal laser scanning microscopy and image analysis to examine the dynamics of anthracycline drugs in cancer cells. Cytotoxicity determined by MTT dye reduction showed that A2780AD cells were more than 400 times less sensitive to doxorubicin compared to A2780 cells but almost 9 times more sensitive to ME2303 compared to doxorubicin. The naturally fluorescent drug was tracked within live cells at 37 degrees C to provide time-course information in relation to nuclear and Golgi-associated cellular domains, as indicated by BODIPY FL ceramide-associated fluorescence. In both cell types, ME2303 was characterised by strong nuclear membrane and perinucleolar fluorescence and as a localised punctate pattern within the nucleus. A2780AD cells accumulated ME2303 in their nuclei at a much reduced rate compared to the doxorubicin-sensitive cells, and ME2303 efflux from resistant cell nuclei was approximately twice as fast as from A2780 cells. The relative uptake of ME2303 into Golgi-associated domains and the nucleus were monitored simultaneously during the initial 35 min of exposure to 10 microM ME2303 and during the first 45 min of a "chase" culture following exposure to 20 microM ME2303. ME2303 was detectable within the Golgi-associated domains of A2780 cells several minutes later and in less relative concentration than in A2780AD cells 15 min into a chase culture. Our results suggest the direct involvement of differences in drug processing via the Golgi apparatus in the expression of P-glycoprotein-related drug resistance.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Huxham IM,Barlow AL,Lewis AD,Plumb J,Mairs RJ,Gaze MN,Workman P

doi

10.1002/ijc.2910590118

subject

Has Abstract

pub_date

1994-10-01 00:00:00

pages

94-102

issue

eissn

0020-7136

issn

1097-0215

journal_volume

pub_type

杂志文章

在线工具

Differential intracellular processing of the anthracycline drug ME2303 in doxorubicin-sensitive (A2780) and -resistant (A2780AD) human ovarian cancer cells as studied with confocal laser scanning microscopy and image analysis.