Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China; Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China; Department of Pharmacology, Faculty of Pharmacy, University of Gezira, Wad-Medani, Sudan.
Phytomedicine. 2018 Feb 1;40:140-147. doi: 10.1016/j.phymed.2018.01.008. Epub 2018 Jan 31.
Colorectal cancer (CRC) is one of the most common malignancies associated with high mortality rate worldwide. We previously reported that pristimerin inhibits cell growth and induces apoptosis in CRC cells.
HYPOTHESIS/PURPOSE: To further understand the molecular mechanism by which pristimerin elicits its anticancer activities on colon cancer cells, we investigated its effect on nuclear factor-κB (NF-κB) signaling pathway.
This study consisted of both in vitro and in vivo experiments involving HCT-116 cell line and xenograft mouse model. Molecular techniques such as qRT-PCR, western blotting and immunofluorescence were used to demonstrate pristimerin in vitro effect on NF-κB signaling pathway; whereas it's in vivo activity was analyzed by western blot and immunohistochemistry on tumor tissues.
Our in vitro results on HCT-116 cells showed that pristimerin inhibited IKK phosphorylation, IкB-α degradations and IкB-α phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-кB p65 phosphorylation, nuclear translocation and accumulation of NF-кB. Moreover, pristimerin was found to inhibit both constitutive activated-NF-кB and tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-induced activation of NF-кB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that pristimerin inhibited tumor growth mainly through suppressing NF-кB activity in tumor tissues.
Pristimerin antitumor activities were mainly mediated through inhibition of NF-кB signaling pathway in colon tumor cells. These findings further explain that pristimerin has the therapeutic potential for targeting colon cancer.
结直肠癌（CRC）是全球死亡率较高的最常见恶性肿瘤之一。我们之前报道过，白屈菜春碱可抑制 CRC 细胞的生长并诱导其凋亡。
假说/目的：为了进一步了解白屈菜春碱发挥其抗癌活性对结肠癌的分子机制，我们研究了其对核因子-κB（NF-κB）信号通路的影响。
本研究包括体外和体内实验，涉及 HCT-116 细胞系和异种移植小鼠模型。采用 qRT-PCR、western blot 和免疫荧光等分子技术，证明白屈菜春碱在体外对 NF-κB 信号通路的作用；而在肿瘤组织上通过 western blot 和免疫组化分析其体内活性。
我们在 HCT-116 细胞上的体外结果表明，白屈菜春碱以剂量和时间依赖的方式抑制 IKK 磷酸化、IкB-α降解和 IкB-α磷酸化，从而抑制 NF-кB p65 磷酸化、核转位和 NF-кB 积累。此外，白屈菜春碱被发现可抑制组成性激活的 NF-кB 以及肿瘤坏死因子-α（TNF-α）和脂多糖（LPS）诱导的 NF-кB 信号通路的激活。此外，我们在异种移植动物模型上的体内结果表明，白屈菜春碱主要通过抑制肿瘤组织中的 NF-кB 活性来抑制肿瘤生长。
白屈菜春碱的抗肿瘤活性主要通过抑制结肠肿瘤细胞中的 NF-κB 信号通路来介导。这些发现进一步表明，白屈菜春碱具有针对结肠癌的治疗潜力。
