Objective: To investigate the co-expression of drug resistance- and apoptosis-related genes of cisplatin （CDDP）-selected lung adenocarcinoma cell line A549DDP for compared to the parental cell line A549, and reverse of drug resistance by antisense s-oligodeoxynucleotides （S-ODNs） of differentially expressed genes. Methods: Sense and antisense S-ODN were transferred into A549DDP cells by lipofectin. The expression of drug resistance and apoptosis related genes was examined by RT-PCR, immunocytochemistry and flow cytometry, respectively. Apoptostic cells were identified by DNA electrophoresis and terminal deoxynucleotidyl transferase （TdT）-mediated biotin dUTP nick end- labeling（TUNEL）. Drug resistance of tumor cells was detected by a cell viability （MTT） assay. Results: The expression of bc1-2 was positive and that of multidrug resistance-associated protein （MRP） at mRNA and protein level was increased in A549DDP compared to A549 cells. MDRI, c-myc and topoisomeras Ⅱ （TOPO Ⅱ） were similarly co-expressed in two cell lines. Both cell lines were negative for c-erbB-2 expression. In A549DDP cells, the expression of bc1-2 and MRP was sigllificantly inhibited by their respective antisense S-ODNs. Antisensc S-ODNs could also decrease significantly drug resistance of A549DDP cells to CDDP by promoting cell apoptosis. Conclusion: Both intrinsic and acquired drug resistance were involved in co-expression of multiple MDR-related genes in lung adenocarcinoma. Co- operation of hcf-2 and MRP genes appeared to play an important action to confer the resistance of A549DDP cells to CDDP. Their antisense S-ODNs are responsible for the decrease of drug resistance of this cell line by promoting apoptosis.
