Eicher S A, Lotan R
Department of Head and Neck Surgery, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Laryngoscope. 1996 Dec;106(12 Pt 1):1471-5. doi: 10.1097/00005537-199612000-00005.
Both retinoic acid (RA) and the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) have shown efficacy in head and neck cancer chemoprevention trials. To compare their activity and mechanism of action, the 1483 oral head and neck squamous cell carcinoma (HNSCC) cell line was grown in organotypic culture, an in vitro system that allows cellular stratification and simulates carcinoma in situ, and was exposed to 10 micromol/L of either RA or 4HPR. Extensive apoptosis, as evidenced by in situ deoxyribonucleic acid end-labeling, occurred in 4HPR-treated cultures after 9 days, with >80% cell loss (P< .001). In contrast, the growth of cultures treated with RA was inhibited by only 32%, with no evidence of apoptosis. Because 4HPR has low systemic toxicity and is a potent inducer of apoptosis in HNSCC cells, its role in chemoprevention of head and neck cancers, including cancers that are resistant to RA-induction therapy, warrants further investigation.
维甲酸（RA）和合成类视黄醇N-（4-羟苯基）视黄酰胺（4HPR）在头颈癌化学预防试验中均显示出疗效。为比较它们的活性和作用机制，将1483口腔头颈鳞状细胞癌（HNSCC）细胞系置于器官型培养中生长，这是一种体外系统，可使细胞分层并模拟原位癌，然后将其暴露于10微摩尔/升的RA或4HPR中。经原位脱氧核糖核酸末端标记证明，9天后，4HPR处理的培养物中出现广泛凋亡，细胞损失>80%（P<0.001）。相比之下，RA处理的培养物生长仅受32%抑制，且无凋亡迹象。由于4HPR全身毒性低，是HNSCC细胞凋亡的有效诱导剂，其在头颈癌化学预防中的作用，包括对RA诱导治疗耐药的癌症，值得进一步研究。
