|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|
|WOS标题词||Science & Technology|
|类目[WOS]||Oncology ; Obstetrics & Gynecology|
|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|
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.
|资助机构||General Program of National Natural Science Foundation of PR China|
|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
|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.|