Document Detail

Overexpression of glycogen synthase kinase-3 in ovarian carcinoma cells with acquired paclitaxel resistance.
MedLine Citation:
PMID:  21436692     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Acquired resistance to paclitaxel, including regimens, is one of the most significant reasons for treatment failure and death in patients with ovarian cancer, but the causes of this resistance remain unclear. However, cell cycle regulation is a key mechanism by which most chemotherapeutic agents exert their cytotoxic effects.
METHODS: We created a paclitaxel-resistant ovarian carcinoma cell line from SKOV3 cell line, and the difference of cell cycle distribution was analyzed using flow cytometry. Analysis of human cell cycle pathway complementary DNA array was performed to identify candidate genes associated with paclitaxel resistance. Gene expression changes were validated at the messenger RNA and protein levels by real-time reverse transcriptase polymerase chain reaction and Western analysis, respectively.
RESULTS: The ratio of Gap0/Gap1 phase in SKOV3-TR30 was significantly lower than that in SKOV3 (54.8% ± 6.3% vs 72.7% ± 7.6%, P = 0.035), and the ratio of G2/M phase in SKOV3-TR30 was significantly higher than that in SKOV3 (24.9% ± 6.0% vs 10.2% ± 3.5%, P = 0.021). Complementary DNA microarray analysis demonstrated enhanced glycogen synthase kinase-3α (GSK-3α) expression in paclitaxel-resistant ovarian carcinoma cells. Real-time reverse transcriptase polymerase chain reaction analysis revealed that the paclitaxel-resistant subline exhibited a 7.0 ± 1.8-fold increase in GSK-3α messenger RNA expression. There was a 3.34 ± 0.47-fold increase of total GSK-3 protein (GSK-3α/β) in SKOV3-TR30 cells validated by Western analysis.
CONCLUSIONS: This study demonstrates that enhanced expression of GSK-3 is associated with acquired resistance to paclitaxel in ovarian carcinoma cells. Glycogen synthase kinase-3 overexpression may probably be a significant contributor to chemoresistance.
Yunfeng Fu; Dongxiao Hu; Jian Qiu; Xing Xie; Feng Ye; Wei-Guo Lu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of gynecological cancer : official journal of the International Gynecological Cancer Society     Volume:  21     ISSN:  1525-1438     ISO Abbreviation:  Int. J. Gynecol. Cancer     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-25     Completed Date:  2011-08-16     Revised Date:  2012-06-19    
Medline Journal Info:
Nlm Unique ID:  9111626     Medline TA:  Int J Gynecol Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  439-44     Citation Subset:  IM    
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Blotting, Western
Cell Cycle
Drug Resistance, Neoplasm*
Gene Expression Profiling
Glycogen Synthase Kinase 3 / genetics,  metabolism*
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / drug therapy*,  genetics,  metabolism*
Paclitaxel / pharmacology*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Markers, Biological / genetics,  metabolism
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/RNA, Messenger; 0/Tumor Markers, Biological; 33069-62-4/Paclitaxel; EC synthase kinase 3 beta; EC Synthase Kinase 3; EC synthase kinase 3 alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Changes in activities of caspase-8 and caspase-9 in human cervical malignancy.
Next Document:  P16 methylation is an early event in cervical carcinogenesis.