Anti-proliferative activity of fenretinide in human hepatoma cells in vitro and in vivo

作者：Shentu, Jianzhong; Zhang, Bo; Fan, Lingling; He, Qioajun; Yang, Bo; Chen, Zhi^*

来源：Anti-Cancer Drugs, 2007, 18(1): 47-53.

DOI：10.1097/CAD.0b013e32800feeb5

• apoptosis
• fenretinide
• hepatoma cells
• xenograft

N-(4-hydroxyphenyl)-retinamide (fenretinide) is a synthetic derivative of all-trans-retinoic acid and induces apoptosis in several cancer cell lines. We determined the anti-cancer activity of fenretinide using human hepatoma cell lines, Bel-7402, HepG2 and Smmc-7721. An in-vitro 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that fenretinide exhibited growth inhibition in these cell lines, with IC50 values ranging from 13.1 to 15.5 mu mol/l. In Bel-7402 cells, apoptosis with 15 mu mol/l fenretinide for 0 and 48 h was 3 and 48%, respectively. In-vivo studies using the Bel-7402 xenografted athymic mouse model showed tumor inhibition rates ranging from 37.2 to 57.2%, with fenretinide administration once per 3 days at the rate of 25-100 mg/kg. Western blot analysis further showed down-regulation of procaspase-3, X-linked inhibitor of apoptosis protein and poly(ADP-ribose) polymerase cleavage in Bel-7402 cells treated with 15 mu mol/l fenretinide for 48h. Overexpression of p53 was observed in a time-dependent manner, along with a decrease in the Bcl-2/Bax ratio. Depolarized mitochondrial membranes were found in fenretinide-induced apoptotic cells, in a time-dependent manner. We conclude that fenretinide effectively inhibits the proliferation of Bel-7402, both in vitro and in vivo. Both procaspase-3 and p53-mediated apoptotic pathways are involved in its potent anti-cancer activity.

• 出版日期2007-1
• 单位浙江大学