We aimed to examine the therapeutic potential of polysaccharide H-1-2, a bioactive component of Pseudostellaria heterophylla, against pancreatic cancer, as well as to demonstrate the underlying molecular mechanisms. Invasion and migration of pancreatic cells treated with H-1-2 were evaluated. A xenograft tumor mouse model was established to assess the effect of H-1-2 on tumor growth. Expression levels of hypoxic inducible factor-1α (HIF1α) and anterior gradient 2 (AGR2) were measured in pancreatic cells after H-1-2 treatment. Luciferase report and chromatin immunoprecipitation assays were conducted to investigate HIF1α regulation on AGR2. AGR2 expression was re-introduced into pancreatic cells to assess the role of AGR2 as a downstream effector of hypoxia after H-1-2 treatment. H-1-2 inhibited invasion and migration of pancreatic cancer cells, repressed xenograft pancreatic tumor growth, and increased survival of mice. H-1-2 repressed AGR2 expression in pancreatic cancer cells through the hypoxia response element (HRE) in its promoter region. Ectopic AGR2 expression partially negated the H-1-2 inhibitory effect on invasion and migration of pancreatic cells and on xenograft pancreatic tumors growth, and it also compromised the H-1-2 promotional effect on survival of mice. We conclude that H-1-2 suppresses pancreatic cancer by inhibiting hypoxia-induced AGR2 expression, supporting further investigation into its efficacy against pancreatic cancer in clinical settings.

我们旨在检查多糖H-1-2（太子参的生物活性成分）的治疗潜力，针对胰腺癌，以及证明其潜在的分子机制。评价了用H-1-2处理的胰腺细胞的侵袭和迁移。建立异种移植肿瘤小鼠模型以评估H-1-2对肿瘤生长的影响。在H-1-2处理后，测量胰腺细胞中低氧诱导因子-1α（HIF1α）和前梯度2（AGR2）的表达水平。进行了荧光素酶报告和染色质免疫沉淀测定，以研究HIF1α对AGR2的调控。将AGR2表达重新引入胰腺细胞中，以评估AGR2在H-1-2治疗后作为缺氧的下游效应器的作用。H-1-2抑制胰腺癌细胞的侵袭和迁移，抑制异种移植胰腺肿瘤的生长，并增加小鼠的存活率。H-1-2通过其启动子区域的缺氧反应元件（HRE）抑制胰腺癌细胞中AGR2的表达。异位AGR2表达部分抵消了H-1-2对胰腺细胞的侵袭和迁移以及异种移植胰腺肿瘤生长的抑制作用，并且还损害了H-1-2对小鼠存活的促进作用。我们得出的结论是，H-1-2通过抑制缺氧诱导的AGR2表达来抑制胰腺癌，支持对其在临床环境中对抗胰腺癌的功效进行进一步的研究。并且还损害了H-1-2对小鼠存活的促进作用。我们得出的结论是，H-1-2通过抑制缺氧诱导的AGR2表达来抑制胰腺癌，支持对其在临床环境中对抗胰腺癌的功效进行进一步的研究。并且还损害了H-1-2对小鼠存活的促进作用。我们得出的结论是，H-1-2通过抑制缺氧诱导的AGR2表达来抑制胰腺癌，支持对其在临床环境中对抗胰腺癌的功效进行进一步的研究。