HER2/neu Antisense Therapeutics in Human Breast Cancer
Final rept. 1 Aug 1999-31 Jul 2002
WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE
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In order to define mechanisms by which HER2neu overexpression drives breast cancer cell growth and chemoresistance, antisense oligodeoxynucleotides ODNs have been used to down-regulate HER2neu expression in human breast cancer cells. Such antisense ODNs suppress HER2neu mRNA and protein expression in a dose-dependent, sequence-specific manner. Antisense ODN-mediated down-regulation of HER2neu expression in HER2neu- overexpressing breast cancer cells inhibits cell cycle progression in GOGI and results in apoptotic cell death. In tissue culture studies, combined treatment of HER2neu overexpressing breast cancer cells with HER2neu antisense ODNs and conventional chemotherapeutic agents results in synergistic inhibition of cell growth and activation of apoptosis. These studies have been extended to demonstrate synergistic antitumor effects following systemic treatment with HER2neu antisense ODNs and chemotherapeutic agents in breast cancer xenografts in nude mice.
- Medicine and Medical Research