Increase in docetaxel-resistance of ovarian carcinoma-derived RMG-1 cells with enhanced expression of Lewis Y antigen.

Abstract

Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (Le(Y)) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of Le(Y). We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-Le(Y) antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of Le(Y) were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.

• Authors: Fan Zhang, Juanjuan Liu, Bei Lin, Qing Liu, Yue Zhao, Liancheng Zhu, Yingying Hao, Shulan Zhang, Masao Iwamori
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 12 Issue 11 Pg. 7323-34 ( 2011) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 22174601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lewis Blood Group Antigens
• Lewis Y antigen
• Taxoids
• Docetaxel
• Fucosyltransferases
• galactoside 2-alpha-L-fucosyltransferase

Topics

• Apoptosis (drug effects)
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Cell Survival (drug effects)
• Docetaxel
• Drug Resistance, Neoplasm (genetics)
• Female
• Flow Cytometry
• Fucosyltransferases (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Lewis Blood Group Antigens (genetics, metabolism)
• Microscopy, Electron, Transmission
• Neoplasms, Glandular and Epithelial (genetics, metabolism)
• Ovarian Neoplasms (genetics, metabolism)
• Taxoids (pharmacology)
• Transfection