Development of novel cancer drug based on pathway analysis for specific cell death of hepatocellular carcinoma treated with acyclic retinoid

为了阐明去环维A酸类化合物S预防肝癌手术后复发的潜在分子机制，我们研究了去环类维甲酸选择性预防肝癌的靶蛋白。利用无环维A酸类亲和小球的沉淀实验和下一代测序分析，我们分别确定PRDX4和eIF5A以及MAT2A和Cth是有希望的结合蛋白和靶蛋白。我们制备了识别在肝细胞癌中选择性检测到的磷酸化核受体RXRx的抗体。利用这些抗体，我们成功地观察到了肝癌组织中的特定信号。

To clarify underlying molecular mechanism of acyclic retinoid’ s effect to prevent recurrence of hepatocellular carcinoma in patients after surgical removal of the primary tumors, we investigated target proteins of acyclic retinoid responsible for its selective prevention of the cancer. Using precipitation assay with acyclic retinoid-conjugated affinity beads and analyses by next-generation sequencing, we identified PRDX4 and eIF5A, and MAT2A and CTH as promising binding and target proteins, respectively. W e made antibodies recognizing the phosphorylated nuclear receptor, RXRx which was selectively detected in hepatocellular carcinoma. Using these antibodies, we succeeded to observe specific signals in liver cancer tissues.