9-cis-Retinoic Acid is a high-affinity ligand for the retinoic acid receptor (RAR), with an EC50 value of 0.2μM for RARα[1]. 9-cis-Retinoic Acid has been widely used in cell proliferation regulation studies and as a model compound to develop new analytical methods[2].
In vitro, 9-cis-Retinoic Acid treatment (24h) inhibited the cell proliferation of HL-60 cells, with an IC50 value of 30nM[3]. 9-cis-Retinoic Acid treatment (1nM; 20 days) inhibited the growth of SCC-9 cells, accompanied by increased expression of RARα and RARβ[4]. 9-cis-Retinoic Acid treatment (1nM; 5days) resulted in a significant decrease in cell migration, decreased tenascin synthesis, increased G1 phase cell cycle and enhanced α-actin expression in human aortic smooth muscle cells[5].
In vivo, 9-cis-Retinoic Acid treatment (0.08mg/kg/day; i.p.) for 4 weeks reduced the formation of the lymphedema and accelerated the resolution of the tissue swelling in the tails of mice[6]. Treatment with 9-cis-Retinoic Acid (10mg/kg) to male Wistar rats via gavage every other day for 8 weeks reduced the incidence of liver cancer and decreased the liver carcinogenesis index[7].
References:
[1] Heyman R A, Mangelsdorf D J, Dyck J A, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor[J]. Cell, 1992, 68(2): 397-406.
[2] Kane M A. Analysis, occurrence, and function of 9-cis-retinoic acid[J]. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2012, 1821(1): 10-20.
[3] Gottardis M M, Lamph W W, Shalinsky D R, et al. The efficacy of 9-cis retinoic acid in experimental models of cancer[J]. Breast cancer research and treatment, 1996, 38(1): 85-96.
[4] Giannini F, Maestro R, Vukosavijevic T, et al. All‐trans, 13‐cis and 9‐cis retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines: implications for in vivo retinoic acid use[J]. International journal of cancer, 1997, 70(2): 194-200.
[5] Johst U, Betsch A, Wiskirchen J, et al. All-trans and 9-cis retinoid acids inhibit proliferation, migration, and synthesis of extracellular matrix of human vascular smooth muscle cells by inducing differentiation in vitro[J]. Journal of cardiovascular pharmacology, 2003, 41(4): 526-535.
[6] Choi I, Lee S, Kyoung Chung H, et al. 9-cis retinoic acid promotes lymphangiogenesis and enhances lymphatic vessel regeneration: therapeutic implications of 9-cis retinoic acid for secondary lymphedema[J]. Circulation, 2012, 125(7): 872-882.
[7] Silveira E R, Naves M M V, Vannucchi H, et al. Vitamin A and all-trans and 9-cis retinoic acids inhibit cell proliferation during the progression phase of hepatocarcinogenesis in Wistar rats[J]. Nutrition and cancer, 2001, 39(2): 244-251.
9-cis-Retinoic Acid是一种对视黄酸受体(RAR)具有高亲和力的配体，对RARα的EC50值为0.2μM[1]。9-cis-Retinoic Acid已被广泛应用于细胞增殖调控研究，并作为开发新型分析方法的模型化合物[2]。
在体外，用9-cis-Retinoic Acid处理24小时可抑制HL-60细胞增殖，IC50值为30nM[3]。1nM浓度的9-cis-Retinoic Acid处理20天能抑制SCC-9细胞生长，同时伴随RARα和RARβ表达增加[4]。在人主动脉平滑肌细胞中，1nM浓度的9-cis-Retinoic Acid处理5天可显著降低细胞迁移能力、减少腱蛋白合成、增加G1期细胞周期比例并增强α-肌动蛋白表达[5]。
在体内，连续4周每天腹腔注射0.08mg/kg剂量的9-cis-Retinoic Acid可减轻小鼠尾部淋巴水肿形成并加速组织肿胀消退[6]。对雄性Wistar大鼠隔天灌胃给予10mg/kg剂量的9-cis-Retinoic Acid持续8周，能降低肝癌发生率并减小肝脏致癌指数[7]。