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(The FASEB Journal. 2008;22:898.30)
© 2008 FASEB
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(The FASEB Journal. 2008;22:898.30.)
© 2008 FASEB

898.30

Combined targeting of c-myb, c-myc and cdc2 in human colorectal cancer cells

Mohamed Salah I Abaza and Abdul Majeed Bahman

Biological Sciences, Kuwait University, Khaldiya, Kuwait

ABSTRACT

Targeting of growth-promoting genes with antisense oligonucleotides might provide a useful approach to control the abnormal proliferation of cancer cells. In this study, we examined the combined targeting of c-myb, c-myc and cdc2 using antisense oligonucleotides (AS[S]ODNs) in colorectal cancer cell lines. mRNA and protein expression of c-myb, c-myc and cdc2 were drastically reduced following treatment with the corresponding AS[S]ODNs. However, combination antigene therapies targeting c-myb/c-myc, c-myb/cdc2, c-myc/cdc2 or c-myb/c-myc/cdc2 demonstrated greater additive and/or synergistic growth inhibitory effects compared to single antigene therapies. The same combined treatment in the presence of cytotoxic drugs produced a marked inhibition of cancer cell growth compared to treatment with either the combination of AS[S]ODNs alone or cytotoxic drugs alone. Combined targeting of c-myb, c-myc and cdc2 produced a marked apoptotic effect, downregulation of mRNAs of cdk1, cyclin B1, cdk2, cyclin E1, Bcl2 and BclxL and upregulation of mRNAs of p21, Bax and caspase-3 compared to single treatments. These results suggest that combination antigene therapy may provide a promising approach for cancer therapy.





This Article
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