Effect of glutathione S-transferaseπin COC1/Cisplatin cells on cisplatin resistance

Abstract

Objective To study the expression of drug resistance related gene in COC1/Cisplatin (DDP)cell line,and the reversion of cisplatin resistance by antisense oligodeoxynucleotide(ASODN)of the overexpressed gene. Methods The expression of glutathione S-transferaseπ(GSTπ)in COC1/DDP cell line was examined by reverse transcription-polymerase chain reaction(RT-PCR), and compared with that in COC1 cell line.ASODN targeting GSTπwas designed and synthesized.GSTπ-ASODN and missense oligodeoxynucleotide with the concentration of 200 nmol/L were transferred into COC1/DDP cells by lipofectin.The inhibition rate of transferred cells to cisplatin was detected by methyl thiazol tetrazolium(MTT)colori-metric assay,and compared with that in untransferred COC1/DDP cells.And the altered expression of GSTπwas also detected by RT-PCR. Results (1)GSTπwas overexpressed in cisplatin resistant cell line of COC1/DDP as compared with COC1 cell line.(2) In comparison with COC1/DDP cells, GSTπexression in GSTπ-ASODN transfected cells was significantly decreased to 0. 058±0. 022 and resistance index(RI) was 3. 61 (P 0. 05),and the drug sensitivity of COC1/DDP cells either(P> 0. 05). Conclusion (1)The overexpression of GSTπmay play an important role in the induction of resistance of COC1/DDP cells to cisplatin; (2)GSTπ-ASODN can effectively reverse the resistance of COC1/DDP cells to cisplatin and increase their drug sensitivity in a sequence specific manner. Key words: Ovarian neoplasm; Cisplatin; Antisense oligonucleotide; Glutathione S-transferaseπgene; Drug resistance