2026-10-15T01:04:06Z https://www.scidb.cn/oai

10.57760/sciencedb.nprd.00242 2026-07-20T17:08:49Z

2026-07-20 Pregnane alkaloid salonine B targets BCL9 to inhibit hepatocellular carcinoma-Source Data doi:10.57760/sciencedb.nprd.00242 en This study aimed to identify novel BCL9 inhibitors and to investigate their antitumor effects in hepatocellular carcinoma (HCC). Bioinformatic analyses of TCGA and GEO databases revealed that BCL9 was significantly upregulated in HCC tissues, and high BCL9 expression was closely associated with poor prognosis of patients. By establishing stably transfected BCL9-knockdown SK-Hep-1 and BEL-7402 cell lines, we demonstrated that silencing BCL9 markedly suppressed HCC cell proliferation. Based on the crystal structure of the BCL9/β-catenin complex, a computer-aided virtual screening model was constructed, leading to the identification of pregnane alkaloid salonine B, a natural product from Sarcococca saligna. Surface plasmon resonance analysis confirmed that salonine B directly interacts with BCL9 protein in vitro. Cell-based assays, such as MTT and Transwell migration assays, demonstrated that salonine B significantly inhibited the cell proliferation and migration of HCC cells in a BCL9-dependent manner. In a xenograft tumor model, administration of salonine B suppressed tumor growth without significant toxicity. In conclusion, our findings validate BCL9 as a potential therapeutic target for HCC and demonstrate that pregnane alkaloid salonine B exhibits promising anti-HCC activity both in cellular and mouse models, providing a new clue for developing HCC targeted therapy based on natural products, and giving experimental evidence for the active component and its target of the anti-tumor steroidal alkaloids from Sarcococca saligna. salonine B; BCL9; hepatocellular carcinoma; pregnane alkaloid; Wnt/β-catenin Ouyang Xinyu Zhang Linlin Liu Xuesha Cheng Jian Pu Wenchen RESTRICTED dataset Science Data Bank