Therapy of Lung Cancer Based on the Regulation of Gene Expression

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08670640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hokkaido University
• Principal Investigator: AKITA Hirotoshi Hokkaido Univ., Medical Hospital., Lecturer, 医学部・附属病院, 講師 (70222528)
• Project Period (FY): 1996 – 1997
• Keywords: Lung Cancer / Gene Expression / Antisense / Retinoic Acid

Research Abstract

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.