Gynecologic and Obstetric Investigation
Log in to MyKarger to check if you already have access to this content.
Buy
FullText & PDF
Unlimited re-access via MyKarger
Unrestricted printing, no saving restrictions for personal use
read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *
Select
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Learn more
Access via DeepDyve
Unlimited fulltext viewing of this article
Organize, annotate And mark up articles
Printing And downloading restrictions apply
Select
Subscribe
Access to all articles of the subscribed year(s) guaranteed for 5 years
Unlimited re-access via Subscriber Login or MyKarger
Unrestricted printing, no saving restrictions for personal use
read more
Subcription rates
Select
* The final prices may differ from the prices shown due to specifics of VAT rules.
Article / Publication Details
Abstract
Objective: Chemoresistance in ovarian cancer results in treatment failure, yet underlying mechanisms that regulate chemoresistance remain largely unclear. There is emerging evidence relating ovarian cancer drug resistance with bioactive sphingolipids and regulation of sphingolipid metabolism. This work investigated the expression and function of ceramide kinase (CerK), a lipid kinase that regulate central bioactive sphingolipids, in ovarian cancer, as well as the therapeutic potential of targeting CERK. Design: The level of ceramide, C1P and Cerk in ovarian cancer and normal counterpart were measured. Functions of Cerk in ovarian cancer was examined. Materials, Setting, Methods: Immunohistochemistry, ELISA and mass spectrometry methods were used to measure the level of ceramids, C1P and CerK in primary tissues. Proliferation and apoptosis assays were performed in ovarian cancer cells after CERK depletion, CERK overexpression and NVP-231 treatment in the absence or presence of cisplatin. Results: Compared to normal ovarian cells, CerK and its-mediated bioactive sphingolipids ceramide and ceramide 1-phosphate (C1P) were decreased in ovarian cancer tissues. Interestingly, cisplatin-resistant ovarian cancer cells displayed increased CerK, decreased ceramide and increased C1P, and furthermore that CerK level was closely associated with ceramide and C1P levels in ovarian cancer cells. Functional analysis demonstrated that CerK overexpression was sufficient to promote growth and confer chemo-resistance in ovarian cancer cells. CerK inhibition via both genetic and pharmacological approaches suppressed growth and induced apoptosis in cisplatin-resistant cells, and furthermore that significantly augmented cisplatin’s efficacy. Limitations: The functional analysis of C1P was performed in in vitro ovarian cancer cells. In vivo studies were needed to further confirm the effects of CERK inhibition. Conclusions: Our work is the first to show the critical role of CerK as the underlying mechanism of ovarian cancer chemoresistance, through regulating ceramide and C1P.
S. Karger AG, Basel
Article / Publication Details
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
留言 (0)