[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 α1,2-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 μg/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-α(PKC-α),topoismeraseⅠ(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 P0.05). However,the mRNA expression of multidrug 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,P0.05). The P-gp level increased in RMG-I-H cells compared with that in RMG-I cells both in vivo and in vitro (P0.05). Expressions of MDR-1,MRP-1,MRP-2,PKC-α,and TopoⅠ mRNA decreased by the time in RMG-I-H cells treated with anti-Lewis y monoclonal antibody (all P0.05),while mRNA expressions of those genes in the control group did not statistically change (P0.05). In addition,MDR-1,MRP-1,MRP-2,PKC-α,and TopoⅠ 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 P0.05) and the inhibition ratios were 48.55%,77.50%,70.18%,45.86%,and 46.13%,respectively. Conclusion 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.