Therapy of Lung Cancer Based on the Regulation of Gene Expression

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The overexpression of c-myc frequently accmpanies the relapse of small cell lung cancers (SCLCs) and contributes to the poor prognosis of patients with SCLVs. In this tudy, We investigated whether c-myc antisense oligodeoxynucleoside phosphorothioate (OPT) used in combination with all-trans-retinoic acid (RA) could be an experimental therapeutic tool against c-myc in a SCLC cell lime, NCI-H82, overexpressing c-myc with amplification of this gene. A c-myc antisense OPT covering the translational initiation site of c-myc mRNA decreased c-myc expression and inhibited cell growth. AII-trans RA also down-regulated c-myc expression as well as cell growth, as was previously reported. A combination of this antisenes DNA with all-trans-RA exhibited a enhanced reduction of c-myc expression over either agent given alone. Furthermore, this combination showed a greater inhibition of cell growth through c-myc down-regulation than either agent alone.These data suggest that c-myc antisense DNA in combination with RA may represent an attractive modality of gene regulation-based therapy of SCLCs in future, although further efforts are needed for the more potent down-regulation of c-myc.