目的 考察白头翁Pulsatilla chinensis皂苷对人肝癌Bel-7402荷瘤裸鼠异体移植瘤的抑制作用，并从能量代谢角度探讨其作用机制。方法 制备人肝癌Bel-7402裸鼠异体移植瘤模型，通过肿瘤体积、抑瘤率观察白头翁皂苷的体内抗肿瘤活性；生物化学法检测瘤块组织乳酸及ATP的量以观察白头翁皂苷对能量代谢的调节作用；ELISA法检测白头翁皂苷对能量代谢相关酶变化的影响；Western blotting 法检测白头翁皂苷对能量代谢调控蛋白缺氧诱导因子-1α（HIF-1α）的影响。结果 白头翁皂苷能较好地抑制肝癌荷瘤裸鼠异体移植瘤的生长，可明显减小肿瘤体积，白头翁皂苷400、200、100 mg/kg抑瘤率依次为42.8%、31.5%、14.9%，呈剂量依赖关系，且对血液白细胞（WBC）无明显影响；白头翁皂苷能明显降低瘤块组织中乳酸和ATP的量；白头翁皂苷可降低糖酵解关键酶己糖激酶-II（HK-II）、磷酸果糖激酶（PFK）及丙酮酸激酶（PK）的量，提高三羧酸循环关键酶琥珀酸脱氢酶（SDH）的量；Western blotting检测结果显示白头翁皂苷可明显降低瘤块组织HIF-1α蛋白的表达。结论 白头翁皂苷具有较好的体内抗肿瘤作用，其可能通过HIF-1α通路调节肿瘤细胞能量代谢，来达到抑制肿瘤生长的作用。

Objective To investigate the antirumour activity of saponins from Pulsatilla chinensis against the Bel-7402 human hepatocellular carcinoma xenograft in nude mice, and to explore the mechanism of energy metabolism. Methods The antitumor activity in vivo was estimated using a Bel-7402 xenograft model. The tumor volume was measured, the tumor inhibitory rate was calculated, the levels of lactic acid and ATP were assessed in Bel-7402 xenograft in nude mice, energy metabolic enzymes in Bel-7402 xenograft in nude mice were detected by ELISA assay, and hypoxia inducible factor-1 (HIF-1α) was detected by Western blotting assay. Results The sapoinins from P. chinensis could inhibit the growth of Bel-7402 xenograft in a dose-depedent manner. The tumor inhibitory rates at the dose of 400, 200, and 100 mg/kg were 42.8%, 31.5%, and 14.9%. They had no side effects on white blood cell (WBC) in blood; The saponins from P. chinensis could decrease the contents of lactic acid and ATP. They also could decrease the levels of glycolytic enzymes phosphofructokinase (PFK), hexokinase-II (HK-II), and pyruvate kinase (PK), while increase the level of succinatedehydrogenase (SDH) that was the key enzyme during tricarboxylic acid cycle. Western blotting indicated that the expression of HIF-1α protein was significantly decreased in Bel-7402 xenograft in nude mice. Conclusion The saponins from P. chinensis could inhibit the growth of Bel-7402 xenograft in nude mice in vivo, the mechanism is related with regulating energy metabolism through the HIF-1α pathway.

国家“十二五”“重大新药创制”科技重大专项项目（2011ZX09102-001-19）；江西省优势科技创新团队计划项目（2010DQB01700）；江西省教育厅产学研合作项目（GJJ11006）