维甲酸衍生物对肿瘤细胞的凋亡诱导作用

Function of apoptosis induced by derivatives of retinoid acid on tumor cells

维甲酸及衍生物的抗肿瘤作用已在白血病及多种实体肿瘤的临床治疗及实验室研究中显示出其诱人前景。其中,较引人注目的是一系列新的维甲酸衍生物,如CD437,ST1926,MM002等。这些新发现的维甲酸衍生物较目前临床应用较广的全反式维甲酸(ARTA)有更强的凋亡诱导作用,更低的细胞毒性和更理想的药物代谢动力学指标,诱导凋亡途径也不同于传统维甲酸类药物作用依赖p53激活的途径。其作用的分子机制也完全有别于目前已知的化疗药物,可诱导对维甲酸和其它多种化疗药物耐药的肿瘤细胞发生凋亡。该文对目前维甲酸衍生物在肿瘤细胞中的凋亡诱导作用研究作一综述。

Retinoid acid and its derivatives have shown promising perspective in clinical use and lab research on the leukemia and other solid tumor cells. Some of these compounds have a stronger apoptotic potential, a lower level of cytotoxicity and a better pharmacokinetic profile than all-trans retinoic acid. The apoptosis pathways induced by these compounds are different from traditional p53-dependent pathway which recruited by many chemotherapeutics. Due to its specific molecular mechanism, these compounds could induce apoptosis in retinoic acid- resistant or multi-drug- resistant tumor cells. This paper reviews the current research on apoptosis induced by analogues of retinoid acid.