Combination antigene therapy targeting c-myc and c-erbB(2) in the ovarian cancer COC(1) cell line.
OBJECTIVE
Antigene therapy targeting only one oncogene in ovarian cancer has made much progress, although it still has some limitations. To explore the potential for combination antigene therapy in ovarian cancer, we examined the in vitro effects of liposmal antisense phosphorothioate oligodeoxynucleotides targeting c-erbB(2) and c-myc (LF-c-erbB(2)/c-myc AS-ODNs) in the human ovarian cancer COC(1) cell line.


METHODS
COC(1) cells were treated differently as follows: group A with single LF-c-erbB(2) AS-ODNs; group B with single LF-c-myc AS-ODNs; group C with combination LF-c-erbB(2)/c-myc AS-ODNs; and group D as untreated control. Cell proliferation was studied by MTT assay and clonal cultures. RT-PCR was used to measure gene expression of c-erbB(2) and c-myc before and after transfection. Morphologic changes in the COC(1) cells were observed with the electron microscope.


RESULTS
Single antigene therapy targeting c-erbB(2) or c-myc could reduce target gene expression and inhibit COC(1) cell growth by 61.9 +/- 9.3 and 64.5 +/- 11.2%, respectively. However, combination antigene therapy could not only suppress expression of c-erbB(2) and c-myc simultaneously, but also inhibit COC(1) cell proliferation with a higher inhibitory rate of 82.6 +/- 12.1%. Apart from that, the combination agents could induce COC(1) cell apoptosis.


CONCLUSIONS
Our study suggests that combination antigene therapy targeting c-erbB(2) and c-myc can inhibit COC(1) cell proliferation and gene expression of c-erbB(2) and c-myc. Furthermore, its effectiveness is much higher than that of individual antigene therapy.
Fei
Ruan
R
Department of Gynecologic Oncology, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, 430071, People's Republic of China.
Shaoyang
Liu
L
D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018734:Genes, erbB-2 / Q000187:drug effects* / Q000235:genetics; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000628:therapy*; D013873:Thionucleotides / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides