Yan Li, Liu Xiaolin, Yin Aijun, Wei Yuyan, Yang Qifeng, Kong Beihua
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
Department of General Surgery, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
Int J Oncol. 2015 Sep;47(3):1054-60. doi: 10.3892/ijo.2015.3094. Epub 2015 Jul 20.
Although the anticancer effects of Huaier extract have been widely investigated, including anti-proliferate, anti-angiogenic and anti-metastatic activities, the mechanisms are not well understood. This study aimed to elucidate the inhibitory effect of Huaier extract on tumor growth in cervical cancer cells and its molecular mechanisms. Cell viability and motility were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony assays, migration, and invasive assays, respectively. The distribution of the cell cycle was analyzed by flow cytometry. Huaier inhibited cell viability of SiHa and C33A cells in a time- and dose-dependent manner; cell migration and invasiveness were also suppressed; Huaier was able to cause G2/M cell cycle arrest in C33A cells. The western blot results confirmed Huaier dose-dependently increased expression of phosphorylated c-Jun N-terminal kinase (JNK), p-38 and downregulated the expression of phosphorylated extracellular signal-regulated kinase (ERK) in a time- and dose-dependently manner. In vivo experiments showed that Huaier significantly suppressed the tumor volume of SiHa cell xenografts. These data suggest that Huaier may inhibit tumor proliferation in cervical cancer via the JNK/p38 signaling pathway.
尽管槐耳提取物的抗癌作用已得到广泛研究,包括抗增殖、抗血管生成和抗转移活性,但其机制尚不完全清楚。本研究旨在阐明槐耳提取物对宫颈癌细胞肿瘤生长的抑制作用及其分子机制。分别通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法、集落形成试验、迁移试验和侵袭试验来检测细胞活力和运动能力。通过流式细胞术分析细胞周期分布。槐耳以时间和剂量依赖性方式抑制SiHa和C33A细胞的活力;细胞迁移和侵袭能力也受到抑制;槐耳能够使C33A细胞发生G2/M期细胞周期阻滞。蛋白质印迹结果证实,槐耳能以时间和剂量依赖性方式使磷酸化c-Jun氨基末端激酶(JNK)、p-38的表达剂量依赖性增加,并使磷酸化细胞外信号调节激酶(ERK)的表达下调。体内实验表明,槐耳能显著抑制SiHa细胞异种移植瘤的肿瘤体积。这些数据表明,槐耳可能通过JNK/p38信号通路抑制宫颈癌的肿瘤增殖。