Zhai Huiyuan, Hu Sanyuan, Liu Tongxiang, Wang Feng, Wang Xixun, Wu Guochang, Zhang Yifei, Sui Minghua, Liu Huantao, Jiang Lixin
Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Emergency, People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China.
Mol Med Rep. 2016 Mar;13(3):2536-42. doi: 10.3892/mmr.2016.4827. Epub 2016 Jan 29.
Nitidine chloride (NC) is a natural bioactive phytochemical alkaloid that has displayed anticancer activity in various types of cancer. However, no evidence has been reported for the direct effect of NC on CRC cell proliferation and apoptosis, and the underling mechanisms to be fully elucidated. The present study aimed to investigate the influence of NC on the apoptosis and proliferation of CRC cells. The viability and proliferation of CRC cells was measured by MTT assay and a [3H] thymidine uptake assay. Apoptosis was measured using a flow cytometric apoptosis assay and TUNEL staining. The expression levels of apoptotic‑regulated proteins in addition to extracellular signal‑regulated kinase (ERK) were measured by western blot analysis following stimulation with NC. The results indicated that NC inhibited the proliferation of HCT116 cells in a dose‑ and time‑dependent manner. Additionally, apoptotic induction by NC treatment was confirmed. Furthermore, NC was demonstrated to significantly upregulate the expression of Bax, p53, cleaved caspase‑3 and ‑9 and downregulate the expression of Bcl‑2. Treatment with NC reduced the phosphorylation of ERK and by using an ERK inhibitor, U0126, the roles of NC in apoptotic induction and the inhibition of proliferation were further demonstrated. These results demonstrated that NC inhibited the proliferation and induced the apoptosis of CRC cells via the ERK signaling pathway.
氯化两面针碱（NC）是一种天然的具有生物活性的植物化学生物碱，已在多种癌症类型中显示出抗癌活性。然而，尚无关于NC对结直肠癌细胞增殖和凋亡的直接影响以及相关潜在机制的报道，这些机制有待充分阐明。本研究旨在探讨NC对结直肠癌细胞凋亡和增殖的影响。采用MTT法和[3H]胸腺嘧啶核苷摄取试验检测结直肠癌细胞的活力和增殖情况。使用流式细胞术凋亡检测和TUNEL染色检测细胞凋亡。在用NC刺激后，通过蛋白质印迹分析测定凋亡调节蛋白以及细胞外信号调节激酶（ERK）的表达水平。结果表明，NC以剂量和时间依赖性方式抑制HCT116细胞的增殖。此外，证实了NC处理可诱导细胞凋亡。此外，NC被证明可显著上调Bax、p53、裂解的半胱天冬酶-3和-9的表达，并下调Bcl-2的表达。用NC处理可降低ERK的磷酸化，并且通过使用ERK抑制剂U0126，进一步证明了NC在诱导细胞凋亡和抑制增殖中的作用。这些结果表明，NC通过ERK信号通路抑制结直肠癌细胞的增殖并诱导其凋亡。
