Department of Biomedical Sciences, College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea.
Int J Oncol. 2012 Feb;40(2):452-60. doi: 10.3892/ijo.2011.1204. Epub 2011 Sep 20.
Chemoprevention through the use of food and plants has emerged as a novel approach to control various malignancies including cancer. Pulsatilla koreana extract (PKE) has been used to treat malaria and dysentery. The functions and effect of PKE in cancer treatment have been reported but with less information. In this study, we investigated the effect of PKE on the progression of hepatocellular carcinoma (HCC) cells and its mechanism. PKE strongly suppressed the growth of HCC cells in a dose-dependent manner. Apoptosis by PKE was observed by DAPI and TUNEL staining and accompanied with increases of cleaved PARP and caspase-3 in Huh-7 cells. Also, PKE decreased the expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs). In addition, PKE potently suppressed in vivo neovascularization in a mouse Matrigel plug assay. Furthermore, in vivo study showed that PKE significantly inhibited tumor growth in a mouse xenograft model, and induced apoptosis by increasing the cleaved PARP and caspase-3. The expressions of Ki-67, VEGF, and CD31 in the tumor tissue were decreased by the treatment of PKE. Taken together, our study demonstrates that PKE not only induced apoptosis but also inhibited cell growth and angiogenesis of human HCC. We suggest that PKE is an effective chemotherapeutic candidate for cancer therapy against HCC.
通过使用食物和植物进行化学预防已成为控制各种恶性肿瘤（包括癌症）的新方法。白头翁提取物（PKE）已被用于治疗疟疾和痢疾。已经报道了 PKE 在癌症治疗中的功能和作用，但信息较少。在这项研究中，我们研究了 PKE 对肝细胞癌（HCC）细胞进展的影响及其机制。PKE 以剂量依赖性方式强烈抑制 HCC 细胞的生长。通过 DAPI 和 TUNEL 染色观察到 PKE 诱导的细胞凋亡，并伴随着 Huh-7 细胞中裂解的 PARP 和 caspase-3 的增加。此外，PKE 降低了缺氧诱导因子（HIF-1α）和血管内皮生长因子（VEGF）的表达，并抑制了人脐静脉内皮细胞（HUVEC）的管形成和迁移。此外，PKE 在小鼠 Matrigel plugs 实验中强烈抑制体内新生血管形成。此外，体内研究表明，PKE 在小鼠异种移植模型中显著抑制肿瘤生长，并通过增加裂解的 PARP 和 caspase-3 诱导细胞凋亡。PKE 处理降低了肿瘤组织中 Ki-67、VEGF 和 CD31 的表达。总之，我们的研究表明，PKE 不仅诱导细胞凋亡，而且还抑制人 HCC 的细胞生长和血管生成。我们认为 PKE 是治疗 HCC 的有效化学治疗候选药物。
