The Effect of All-trans-retinoic Acid on the Cell Cycle of Head and Neck Squamous Cell Carcinomas / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVE: Retinoids, including vitamin A and its synthetic analogs, are known to suppress carcinogenesis in various epithelial tissues and also to inhibit the cell growth of head and neck squamous cell carcinomas (HNSCC). However, the exact mechanism of retinoids is not yet known. The aim of this study is to investigate the effect of all-trans-retinoic acid (RA) on the cell cycle in HNSCCs and to see if the inhibition of cell growth by RA is due to the arrest of cell cycle. MATERIALS AND METHODS: For in vitro study, AMC-HN-4 and AMC-HN-6 (HNSCC cell lines) were treated with 1 nM of RA and cultured for 6 days. CellTiter 96(TM) AQ(ueous) Non-Reactive Cell Proliferation Assay kit was used to analyze the inhibition of cell growth. Flow cytometric analysis was performed for cell cycle analysis. For in vivo study, AMC-HN-4 and AMC-HN-6 were injected subcutaneously into athymic nude mice and RA (20 mg/kg) was orally administered once a day for 30 days. Tumor volumes were measured with digimatic caliper and the cell cycle was analyzed using frozen specimens. RESULTS: The growth of AMC-HN-4 and AMC-HN-6 were inhibited by RA in vitro and in vivo. The inhibitory effect of RA was more significant in AMC-HN-4 than in AMC-HN-6. RA had no significant effect on the cell cycle in the medium containing 10% fetal bovine serum (FBS), but there was a mild increase in the G1 phase in the medium containing 0.5% FBS in vitro. In vivo, the increase in G1 phase was observed in both AMC-HN-4 and AMC-HN-6. Also, G1 arrest was more significant in AMC-HN-4 than in AMC-HN-6. CONCLUSION: This study suggests that RA may induce G1 arrest, which might be associated with the inhibition of cell growth in HNSCCs.