Primary Study On The Targeting Reversal Of Drug Resistance Of COC1/DDP Cell Line To Cisplatin

Objective: To study the expression of drug resistance related genes of CO -C1/DDP cell line,and the reversion of cisplatin resistance by antisense oligode oxynucleotide(ASODN) of the overexpressed genes.Methods: The expression of multidrug resistance protein(MRP2) and glutat -hione s transferase π(GSTTπ) in COC1/DDP cell line was examined by RT-PC-R and western blotting compared with COC1 cell line. Antisense and missense oligodeoxynucleotide were transferred into COC1/DDP cells by lipofectin. The inhibition rate of transferred cells to cisplatin was detected with MTT colori-metric assay compared with untransferred COC1/DDP cells. And the altered expression of MRP2 and GSTπ were also detected by RT-PCR and western blotti -ng.Results: The expression of GSTπ and MRP2 increased at mRNA and prot -ein levels in the cisplatin resistance cells, while the parental cells did not express MRP2 and GST71. In COC1/DDP cells, the expression of GSTπ and MR-P2 was significantly inhibited by antisense SODN. Antisense SODN could als-o significantly enhanced the inhibition effect o-f cisplatin to COC1/DDP cells. On the contrary, missense oligodeoxynucleotide had no effect on inhibition of the expression of MRP2 and GSTπ, and the drug sensitivity of COC1/DDP cells either.Conclusions: (1) The overexpression of GSTπ and MRP2 may play an important role in the induction of resistance of COCl/DDP cells to cisplatin. (2) Both GSTπ-ASODN and MRP2-AS0DN can effectively reverse the resistance of COC1/DDP cells to cisplatin and increase their drug sensitivity in a sequ-ence specific manner.