[Effect of Lewis y antigen on regulating gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H].
OBJECTIVE
To 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.


METHODS
RT-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.


RESULTS
The 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.


CONCLUSIONS
The 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.
Liu
Qing
Q
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
Lin
Bei
B
Wang
Peng-Li
PL
Yan
Li-Mei
LM
Hao
Ying-Ying
YY
Li
Fei-Fei
FF
Zhu
Lian-Cheng
LC
Zhang
Shu-Lan
SL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005647:Fucosyltransferases; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms; D014162:Transfection; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004264:DNA Topoisomerases, Type I; D005647:Fucosyltransferases; D007983:Lewis Blood Group Antigens; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C000715087:ABCC2 protein, human; C094162:Lewis Y antigen; C528909:TOP1 protein, human; C421109:multidrug resistance-associated protein 1