지속적으로 활성화된 FOXO3로 Akt/FOXO3a 신호 전달 억제시 유도되는 갑상선 난포암 성장 억제 효과

Dept. of Medical Science/박사Akt-dependent FOXO3a cytoplasmic translocation is an important tumorigenic mechanism for escaping from apoptosis in cancer cells. In the present study, we examined whether non-phosphorylatable FOXO3a can inhibit cell growth of distinct follicular thyroid carcinoma(FTC) cell lines. Adenovirus carrying the FOXO3a-triple mutant (TM) sequence including point mutations at three Akt phosphorylation sites (Ad-FOXO3a-TM) was generated and transduced to the cells to mimic inhibition of Akt/FOXO3a signal. Transduction of Ad-FOXO3a-TM to FTC cells induced cell cycle arrest and apoptosis. Intratumor injection of Ad-FOXO3a-TM suppressed the growth of xenograft tumors induced in athymic mice by FTC133 cells. Consequently, our results indicate that gene therapy based on Ad-FOXO3a-TM resulting in constitutively activated FOXO3a signaling has therapeutic potential for FTC.ope