IMR OpenIR
Comparative evaluation of the effects of 5-Aza-2'-deoxycytidine and Trichostatin A on reactivation of hMLH1 in COC1/DDP ovarian cancer cell line
Alternative TitleComparative Evaluation of the Effects of 5-Aza-2'-deoxycytidine and Trichostatin A on Reactivation of hMLH1 in COC1/DDP Ovarian Cancer Cell Line
Meng Chunfeng; Dai Dongqiu; Guo Kejun
2009
Source PublicationCHINESE JOURNAL OF CANCER RESEARCH
ISSN1000-9604
Volume21Issue:2Pages:102-108
AbstracthMLH1 protein serves to detect the DNA damage caused by cisplatin (DDP) and destroys the cell. The absence of hMLH1 expression has been correlated with acquired resistance of ovarian cancer cells to platinum. The aim of this study was to determine the possible role of DNA methylation and histone H3 lysine 9 (H3-K9) acetylation on the loss of hMLH1 expression, and to evaluate the reversal effects of 5-Aza-2'-deoxycytidine (5-Aza-dC) and Trichostatin A (TSA) on DDP-resistance in ovarian cancer cell lines.
Other AbstractObjective: hMLH1 protein serves to detect the DNA damage caused by cisplatin (DDP) and destroys the cell. The absence of hMLH1 expression has been correlated with acquired resistance of ovarian cancer cells to platinum. The aim of this study was to determine the possible role of DNA methylation and histone H3 lysine 9 (H3-K9) acetylation on the loss of hMLH1 expression, and to evaluate the reversal effects of 5-Aza-2'-deoxycytidine (5-Aza-dC) and Trichostatin A (TSA) on DDP-resistance in ovarian cancer cell lines.Methods: Two human ovarian cancer cell lines, COC1 and its DDP-resistant subline, COC1/DDP were cultured. The two cancer cells were treated with 5-Aza-dC or TSA. Using COC1 cells as a control, we used methylation-specific PCR (MSP) to analyze DNA methylation at hMLH1 gene promoter. hMLH1 mRNA and protein expressions were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Chromatin immunoprecipitation assay (ChIP) was used to test the levels of histone H3-K9 acetylation at hMLH1 gene promoter.Results: In COC1 cells, there was no DNA methylation at hMLH1 gene promoter, while there were hMLH1 mRNA and protein expression. In COC1/DDP cells, there was DNA hypermethylation at hMLH1 gene promoter, while there was no hMLH1 mRNA or protein expression. The treatment with 5-Aza-dC resulted in DNA demethylation at the promoter region, as well as restoration of hMLH1 expression in COC1/DDP cells. The treatment with TSA had no effects on DNA demethylation or restoration of hMLH1 expression in COC1/DDP cells.Conclusion: Hypermethylation of DNA at the promoter is related to the silencing of hMLH1 in COC1/DDP ovarian cancer cells. DNA methylation at hMLH1 promoter could play a significant role in determining the sensitivity of ovarian cancer to DDP. The drug resistance mediated by methylation of hMLH1 could be overcome by 5-Aza-dC.
KeywordDNA MISMATCH REPAIR METHYLATION GENE TRANSCRIPTION EXPRESSION PROMOTER RESISTANCE BINDING DEMETHYLATION REEXPRESSION Ovarian cancer DNA methylation Drug resistance hMLH1 5-Aza-2 '-deoxycytidine Trichostatin A
Indexed ByCSCD
Language英语
CSCD IDCSCD:3525455
Citation statistics
Document Type期刊论文
Identifierhttp://ir.imr.ac.cn/handle/321006/154452
Collection中国科学院金属研究所
Affiliation中国科学院金属研究所
Recommended Citation
GB/T 7714
Meng Chunfeng,Dai Dongqiu,Guo Kejun. Comparative evaluation of the effects of 5-Aza-2'-deoxycytidine and Trichostatin A on reactivation of hMLH1 in COC1/DDP ovarian cancer cell line[J]. CHINESE JOURNAL OF CANCER RESEARCH,2009,21(2):102-108.
APA Meng Chunfeng,Dai Dongqiu,&Guo Kejun.(2009).Comparative evaluation of the effects of 5-Aza-2'-deoxycytidine and Trichostatin A on reactivation of hMLH1 in COC1/DDP ovarian cancer cell line.CHINESE JOURNAL OF CANCER RESEARCH,21(2),102-108.
MLA Meng Chunfeng,et al."Comparative evaluation of the effects of 5-Aza-2'-deoxycytidine and Trichostatin A on reactivation of hMLH1 in COC1/DDP ovarian cancer cell line".CHINESE JOURNAL OF CANCER RESEARCH 21.2(2009):102-108.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Meng Chunfeng]'s Articles
[Dai Dongqiu]'s Articles
[Guo Kejun]'s Articles
Baidu academic
Similar articles in Baidu academic
[Meng Chunfeng]'s Articles
[Dai Dongqiu]'s Articles
[Guo Kejun]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Meng Chunfeng]'s Articles
[Dai Dongqiu]'s Articles
[Guo Kejun]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.