Study of mechanism of medroxyprogesterone 17-acetate on the cancer stem cell-like properties of human endometrial cancer
10.3760/cma.j.issn.0529-567x.2013.10.012
- VernacularTitle:子宫内膜癌细胞中干细胞样细胞对醋酸甲羟孕酮的抵抗作用及其机制
- Author:
Bingjie LIU
;
Xiaoping LI
;
Lijun ZHAO
;
Jianliu WANG
;
Lihui WEI
- Publication Type:Journal Article
- Keywords:
Endometrial neoplasms;
Medroxyprogesterone 17-acetate;
Drug resistance,neoplasm;
Neoplastic stem cells
- From:
Chinese Journal of Obstetrics and Gynecology
2013;48(10):772-777
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism resistance of medroxyprogesterone 17-acetate (MPA) on the endometrial cancer side-population (SP) cells.Methods (1) Ishikawa-SP cells from endometrial cancer cell lines Ishikawa were be separated by Hoechst 33342 dyeing method and flow cytometry analysis.The clone formation efficiency between Ishikawa-SP cells and Ishikawa-non-SP cells were performed by clone formation assay.Breast cancer resistance protein (BCRP) was examined by immunocytochemistry method.(2)Ishikawa,Ishikawa-SP,Ishikawa-non-SP cells were treated with various concentrations of MPA at 5,10,15,20 μmoL/L.After cultured for 24,48,and 72 hours,cells growth were measured by methanethiosulfomate(MTS) assay.(3) The groups of Ishikawa,Ishikawa-SP,Ishikawa-non-SP cells incubated with MPA at the half maximal inhibitory concentration(IC50) were selected for cell apoptosis assay by using flow cytometry.After MPA treatment,the expression of caspase-3 was examined by immunocytochemistry method.Results (1)There were few proportion of Ishikawa-SP cells in Ishikawa endometrial carcinoma,which were 2.7％.There were stronger clone formation efficiency for Ishikawa-SP cells than that for Ishikawa-non-SP cells in Ishikawa [(6.02 ± 1.17)％ vs.(0.53 ±0.20)％,P =0.001].And there were higher level expression of BCRP (P =0.001)and also more resistant Taxol and radiation between Ishikawa-SP cells and Ishikawa-non-SP cells.(2)The inhibitory effect of MPA was concentrationdependent and time-dependent.(3)After MPA treatment,the apoptosis rates of Ishikawa-SP,Ishikawa-nonSP,Ishikawa were (4.01 ± 0.43) ％,(9.30 ± 0.67) ％,and (4.64 ± 0.18) ％,respectively (P ＜ 0.05).The level expression of caspase-3 in Ishikawa group after MPA treated were higher than that in Ishikawa-SP group.Conclusion MPA may be inhibit the growth of endometrial cancer,Ishikawa-SP and Ishikawa-nonSP cells,while Ishikawa-SP may be more resistant to MPA than Ishikawa-non-SP,which mechanism of resistance on MPA may be related to the properties of cancer stem-like cells and cell apoptosis.
