Search for the molecular mechanism of action of a novel synthetic retinoid, acyclic retinoid

无环类维甲酸（ACR）是一种新型的合成类维甲酸，可预防原发性肿瘤手术切除后肝癌的复发，但其发挥抗肿瘤作用的分子机制尚不清楚。在本研究中，我们发现ACR对人肝癌细胞的生长抑制与诱导p21^<CIP1>和抑制cyclin D1的表达有关。我们还发现ACR激活人肝癌、头颈部和食管鳞状细胞癌中视黄酸受体β并诱导p21^<CIP1>的转录激活。ACR的这些新作用提示该药物可用于各种恶性肿瘤的化学预防和治疗。此外，ACR和OSI461 （exisulind的一种强效衍生物）联合使用可协同抑制HepG2细胞的生长。这一结果提示ACR与OSI461联合应用可能是人类肝癌及其他恶性肿瘤化疗预防和化疗的有效方案。

Acyclic retinoid(ACR), a novel synthetic retinoid, can prevent the recurrence of hepatomas after surgical resection of primary tumors, but the molecular mechanisms by which ACR exerts anti-tumor effects are not known. In the present studies we found that growth inhibition of human hepatoma cells by ACR is associated with induction of p21^<CIP1> and inhibition of expression of cyclin D1. We also found that ACR activates retinoic acid receptor β and induces transcriptional activation of p21^<CIP1> in human hepatoma, and head and neck and esophageal squamous cell carcinoma cells. These novel effects of ACR suggest that this agent might be useful in the chemoprevention and therapy of various malignancies. Furthermore, the combination of ACR and OSI461, a potent derivative of exisulind, exerted synergistic inhibition of the growth of HepG2 cells. This result suggests that the combination of ACR and OSI461 might be an effective regimen for the chemoprevention and chemotherapy of human hepatoma and possibly other malignancies.