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 Title | Comparative 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 Publication | CHINESE JOURNAL OF CANCER RESEARCH
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ISSN | 1000-9604 |
Volume | 21Issue:2Pages:102-108 |
Abstract | 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. |
Other Abstract | Objective: 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. |
Keyword | DNA 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 By | CSCD |
Language | 英语 |
CSCD ID | CSCD:3525455 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.imr.ac.cn/handle/321006/154455 |
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. |
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