Expression and reversion of drug resistance and apoptosis related genes of a DDP resistant lung adenocarcionma cell line A_(549)~(DDP)

Objective To study the expression of drug resistance and apoptosis related genes of A 549 DDP cells as compared to the parental cell line A 549 , and its reversion by antisense s oligodeoxynucleotide (S ODN) of the differentially expressed genes.Methods Sense and antisense S ODN were transferred into A 549 DDP cells by lipofectin. Expression of genes related to drug resistance and apoptosis was examined by RT PCR, immunocytochemitry and flow cytometry. Apoptosis was identified by DNA electrophoresis and TUNEL, and cell growth by MTT uptake.Results The expression of bcl 2 was positive and that of MRP at mRNA and protein levels was increased in A 549 DDP cells compared to A 549 cells. MDR1, c myc and TOPOⅡ were similarly expressed in the two cell lines. Both cell lines were negative for c erbB 2 expression. In A 549 DDP cells, the expression of bcl 2 and MRP was significantly inhibited by respective antisense S ODN. Antisense S ODN could also significantly inhibit proliferation of A 549 DDP cells, and promote cell apoptosis by reducing its resistance to cisplatin.Conclusion Bcl 2 and MRP genes are responsible for the induced resistance of A 549 DDP cells to cisplatin.