Effect of Lewis y antigen on regulating gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H.
- Author:
Qing LIU
1
;
Bei LIN
;
Peng-Li WANG
;
Li-Mei YAN
;
Ying-Ying HAO
;
Fei-Fei LI
;
Lian-Cheng ZHU
;
Shu-Lan ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; genetics; metabolism; Animals; Cell Line; Cell Line, Tumor; DNA Topoisomerases, Type I; genetics; metabolism; Drug Resistance, Multiple; Drug Resistance, Neoplasm; genetics; Female; Fucosyltransferases; Gene Expression; Gene Expression Regulation; physiology; Gene Expression Regulation, Neoplastic; physiology; Humans; Lewis Blood-Group System; physiology; Mice; Mice, Nude; Multidrug Resistance-Associated Proteins; genetics; metabolism; Ovarian Neoplasms; Transfection
- From: Acta Academiae Medicinae Sinicae 2009;31(4):481-487
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the influence of Lewis y antigen on the gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H.
METHODSRT-PCR was used to determine the gene expressions of partial drug resistance associated proteins in RMG-I-H cell line transfected with alpha1, 2-fucosyltransferases gene and RMG-I cell line, as well as in RMG-I-H treated with or without anti-Lewis y monoclonal antibody at the concentration of 10 micro/g/ml. The immunocytochemical method was used to detect the expression of P-glycoprotein (P-gp) in RMG-I and RMG-I-H cell lines. RMG-I and RMG-I-H cells were transplanted into nude mice and the expression of P-gp in the tissues was measured by immunohistochemistry.
RESULTSThe mRNA expressions of protein kinase C-alpha (PKC-alpha), topoismerase I ( Topo I ), multidrug resistance-associated protein-1 (MRP-1), and MRP-2 were significantly higher in RMG-I-H cells than those in RMG-I cells (0.46 +/- 0.02 vs. 0.27 +/- 0.05, 0.82 +/- 0.08 vs. 0.52 +/- 0.04, 0.66 +/- 0.07 vs. 0.34 +/- 0.12, and 0.44 +/- 0.08 vs. 0.23 +/- 0.05; all P < 0.05). However, the mRNA expression of multi-drug resistance 1 (MDR-1) was significantly lower in RMG-I-H cells than that in RMG-I cells (0.26 +/- 0.05 vs. 0.45 +/- 0.08, P < 0.05). The P-gp level increased in RMG-I-H cells compared with that in RMG-I cells both in vivo and in vitro (P < 0.05). Expressions of MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA decreased by the time in RMG-I-H cells treated with anti-Lewis y monoclonal antibody (all P < 0.05), while mRNA expressions of those genes in the control group did not statistically change (P > 0.05). In addition, MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA expressions were significantly lower in RMG-I-H cells treated with anti-Lewis y monoclonal antibody than those in the control group at 6 hours (all P < 0.05) and the inhibition ratios were 48.55%, 77.50%, 70.18%, 45.86%, and 46.13%, respectively.
CONCLUSIONThe Lewis y antigen of the human ovarian cancer cell surface is closely correlated with the regulation on the gene expression of partial drug resistance associated proteins.
