[Study of mechanism of medroxyprogesterone 17-acetate on the cancer stem cell-like properties of human endometrial cancer].

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 concentration-dependent and time-dependent. (3)After MPA treatment, the apoptosis rates of Ishikawa-SP, Ishikawa-non-SP,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-non-SP 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.

• Authors: Bing-jie Liu, Xiao-ping Li, Li-jun Zhao, Jian-liu Wang, Li-hui Wei
• Journal: Zhonghua fu chan ke za zhi (Zhonghua Fu Chan Ke Za Zhi) Vol. 48 Issue 10 Pg. 772-7 (Oct 2013) ISSN: 0529-567X [Print] China
• PMID: 24406136 (Publication Type: Journal Article)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Neoplasm Proteins
• Medroxyprogesterone Acetate
• CASP3 protein, human
• Caspase 3

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (metabolism)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Separation
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Endometrial Neoplasms (metabolism, pathology)
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Immunohistochemistry
• Medroxyprogesterone Acetate (administration & dosage, pharmacology)
• Neoplasm Proteins (metabolism)
• Neoplastic Stem Cells (drug effects, metabolism)
• Tumor Stem Cell Assay