Guangxi Colleges and Universities Key Laboratory of Pharmacology, Guilin Medical University, Guilin 541004, China; Department of Pharmacy, The First Naval Hospital of Southern Theater Command, Zhanjiang 524005, Guangdong, PR China.
Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, Shaanxi, PR China.
J Ethnopharmacol. 2019 Jul 15;239:111903. doi: 10.1016/j.jep.2019.111903. Epub 2019 Apr 29.
Saponins of many herbs could inhibit the growth of colorectal cancer cells. In the study, we investigated the effects of Paris saponin Ⅶ (PSⅦ), and elucidated its mechanism in colorectal carcinoma cells and a xenograft mouse model.
HT-29 and HCT-116 cells were treated with different concentrations of PSⅦ (0-100 μM). The effects of PSⅦ on HCT-116 cells were assessed using a microarray. Then, apoptotic cells were detected by flow cytometric analysis and apoptosis related protein expression was evaluated by Western blot. A xenograft model of nude mice was used to assess the effect of PSⅦ in vivo.
MTT assay showed the IC values of PSⅦ for growth inhibition of HT-29 and HCT-116 cells were 1.02 ± 0.05 μM and 3.50 ± 0.79 μM respectively. Edu assay demonstrated that PSⅦ effectively suppressed the growth of HT-29 and HCT-116 cells. Treatment with 0-3 μM PSⅦ not only triggered apoptosis, but also activated caspase-3 and caspase-9 of HT-29 and HCT-116 cells in a concentration dependent manner. In parallel to the alterations, Bax and Cyto-c expression increased while Bcl-2 decreased. In nude mice, PSⅦ reduced the tumor size and induced the apoptosis of tumor cells. PSVII could suppress IL-6-induced phosphorylation of STAT3 in vitro and blocked STAT3 phosphorylation in vivo.
Our results suggest that PSVII suppressed the activation of IL-6/STAT3 pathway, consequently suppressed the growth and proliferation and triggered the apoptosis of CRC cells. These findings indicate that PSⅦ might be an effective tumouristatic agent for the treatment of colorectal cancer.
许多草药的皂苷可以抑制结直肠癌细胞的生长。在这项研究中，我们研究了重楼皂苷 VII（PSVII）的作用，并阐明了其在结直肠癌细胞和异种移植小鼠模型中的作用机制。
用不同浓度的 PSVII（0-100μM）处理 HT-29 和 HCT-116 细胞。用微阵列评估 PSVII 对 HCT-116 细胞的影响。然后，通过流式细胞术分析检测凋亡细胞，并用 Western blot 评估凋亡相关蛋白的表达。使用裸鼠异种移植模型评估 PSVII 在体内的作用。
MTT 测定表明 PSVII 对 HT-29 和 HCT-116 细胞生长抑制的 IC 值分别为 1.02±0.05μM 和 3.50±0.79μM。Edu 测定表明 PSVII 有效地抑制了 HT-29 和 HCT-116 细胞的生长。用 0-3μM PSVII 处理不仅能触发细胞凋亡，还能激活 HT-29 和 HCT-116 细胞的 caspase-3 和 caspase-9，且呈浓度依赖性。与此变化平行的是，Bax 和 Cyto-c 的表达增加，而 Bcl-2 减少。在裸鼠中，PSVII 减小了肿瘤体积并诱导了肿瘤细胞的凋亡。PSVII 可在体外抑制 IL-6 诱导的 STAT3 磷酸化，并在体内阻断 STAT3 磷酸化。
我们的结果表明 PSVII 抑制了 IL-6/STAT3 通路的激活，从而抑制了 CRC 细胞的生长和增殖，并触发了细胞凋亡。这些发现表明 PSVII 可能是治疗结直肠癌的有效肿瘤抑制剂。
