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学科主题临床医学
5-Aza-2 ′-Deoxycytidine Improves the Sensitivity of Endometrial Cancer Cells to Progesterone Therapy
Hu, Qian1; Yu, Li1; Chen, Rui1; Wang, Yan-ling2; Ji, Lei2; Zhang, Yan1; Xie, Ya1; Liao, Qin-ping1
关键词Endometrial cancer Progesterone receptor 5-aza-2 &prime -deoxycytidine Medroxyprogesterone acetate DNA methylation
刊名INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2012-07-01
DOI10.1097/IGC.0b013e3182540160
22期:6页:951-959
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Obstetrics & Gynecology
资助者General Program of National Natural Science Foundation of PR China ; General Program of National Natural Science Foundation of PR China
研究领域[WOS]Oncology ; Obstetrics & Gynecology
关键词[WOS]RECEPTOR-B GENE ; HORMONE RECEPTORS ; STEROID-RECEPTORS ; UP-REGULATION ; EXPRESSION ; ADENOCARCINOMA ; DECITABINE ; LINES ; HYPERMETHYLATION ; PROLIFERATION
英文摘要

Objective: Progesterone has been proven to have limited effects on endometrial cancers (ECs), mainly owing to the down-regulation of progesterone receptor (PR). Here, we explored whether 5-aza-2′-deoxycytidine (5-aza-CdR), a demethylating agent, could enhance the susceptibility of EC cells to medroxyprogesterone acetate (MPA).

Methods: Ishikawa and KLE cell lines were treated with 5-aza-CdR and/or MPA. The expression of PR, PR target genes, and matrix metalloproteinase (MMP) was investigated by real-time polymerase chain reaction and Western blot. Promoter methylation was detected by methylation-specific polymerase chain reaction. The effects of 5-aza-CdR and/or MPA on cell proliferation, apoptosis, and invasion of EC cells were evaluated by 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium assay, flow cytometry, invasion assay, and gelatin zymography, respectively.

Results: 5-Aza-2′-deoxycytidine significantly increased the expression of PR and its downstream targets by demethylating PR promoter in both Ishikawa and KLE cells. 5-Aza-2′-deoxycytidine combined with MPA synergistically suppressed the EC cell growth by inducing cell cycle arrest at G2/M phase and apoptosis. Furthermore, 5-aza-CdR synergized with MPA to inhibit the invasion of EC cells, perhaps owing to the down-regulation of MMP-2 and MMP-9 expression and activity.

Conclusions: 5-Aza-2′-deoxycytidine and MPA synergistically inhibit EC cell growth and invasion. Their combined use may provide a new effective therapeutic opportunity for endometrial carcinoma.

语种英语
所属项目编号30672225
资助者General Program of National Natural Science Foundation of PR China ; General Program of National Natural Science Foundation of PR China
WOS记录号WOS:000305908800008
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63442
专题北京大学第一临床医学院
作者单位1.Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100034, Peoples R China
2.Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Hu, Qian,Yu, Li,Chen, Rui,et al. 5-Aza-2 ′-Deoxycytidine Improves the Sensitivity of Endometrial Cancer Cells to Progesterone Therapy[J]. INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER,2012,22(6):951-959.
APA Hu, Qian.,Yu, Li.,Chen, Rui.,Wang, Yan-ling.,Ji, Lei.,...&Liao, Qin-ping.(2012).5-Aza-2 ′-Deoxycytidine Improves the Sensitivity of Endometrial Cancer Cells to Progesterone Therapy.INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER,22(6),951-959.
MLA Hu, Qian,et al."5-Aza-2 ′-Deoxycytidine Improves the Sensitivity of Endometrial Cancer Cells to Progesterone Therapy".INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 22.6(2012):951-959.
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