Objective: To study the expression of drug resistance- and apoptosis-related genes of A549DDP cells as compared to the parental cell line A549, and its reversion by antisense s-oligodeoxynucleotide (S-ODN) of the differentially expressed genes.
Methods: Sense and antisense S-ODN were transferred into A549DDP cells by lipofectin. Expression of genes related to drug resistance and apoptosis was examined by RT-PCR, immunocytochemistry 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 A549DDP cells compared to A549 cells. MDR1, c-myc and TOPO II were similarly expressed in the two cell lines. Both cell lines were negative for c-erbB-2 expression. In A549DDP 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 A549DDP cells, and promote cell apoptosis by reducing its resistance to cisplatin.
Conclusion: Bcl-2 and MRP genes are responsible for the induced resistance of A549DDP cells to cisplatin.