[Expression and reversion of drug resistance- and apoptosis-related genes of a DDP-resistant lung adenocarcinoma cell line A549DDP].
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.


CONCLUSIONS
Bcl-2 and MRP genes are responsible for the induced resistance of A549DDP cells to cisplatin.
Wang
J
J
Department of Internal Medicine, School of Oncology, Beijing Medical University, Beijing 100036.
Liu
X
X
Wu
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017209:Apoptosis / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger