Icariin exerts inhibitory effects on the growth and metastasis of KYSE70 human esophageal carcinoma cells via PI3K/AKT and STAT3 pathways
Icariin exerts inhibitory effects on the growth and metastasis of KYSE70 human esophageal carcinoma cells via PI3K/AKT and STAT3 pathways
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DOI：
10.1016/j.etap.2017.06.004
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发表时间：
2017-09-01
影响因子：
4.3
通讯作者：
Xu, Bao-Bin
中科院分区：
文献类型：
--
作者：
Gu, Zhen-Fang;Zhang, Zi-Teng;Xu, Bao-Bin
食管癌是地球仪中癌症相关死亡率的主要原因之一。目前的治疗选择是不够的，并与副作用的数量。因此，迫切需要开发有效和更有效的食管癌治疗策略。因此，天然产物被认为是开发癌症化疗药物的潜在候选者。淫羊藿苷是一种天然存在的黄酮醇葡萄糖苷，据报道具有从神经保护到抗癌活性的巨大药理学潜力。然而，淫羊藿苷在食管癌中的药理作用在很大程度上仍不清楚。本研究评价了淫羊藿苷对KYSE 70食管癌细胞的抗肿瘤活性，并探讨了其可能的作用机制。淫羊藿苷在食管癌细胞中诱导细胞毒性，IC 50为40 μ M。这些抑制作用是由于细胞凋亡通过活性氧（ROS）介导的线粒体膜电位（MMP）的改变。结果表明，淫羊藿苷在100 μ M时可使ROS增加260%，使MMP降低48%。淫羊藿苷还诱导G2/M细胞周期停滞，这从KYSE 70食管癌细胞的G2细胞群的显著增加中可以看出。此外，淫羊藿苷通过调节上皮间质转化（EMT）标志物的表达抑制食管癌细胞的迁移、侵袭和转移。结果还表明，淫羊藿苷通过抑制PI 3 K/AKT和STAT 3途径部分降低细胞活力和迁移。总之，我们的研究结果表明，淫羊藿苷可能被证明是一个潜在的天然抗癌分子对食管癌。
Esophageal cancer is one of the leading causes of cancer related mortality across the globe. The current treatment options are insufficient and are associated with number of side effects. Therefore there is a pressing need to develop effective and more efficient strategies for the treatment of esophageal cancer. Consistently, natural products are considered potential candidates for develop of cancer chemotherapy. Icariin is a naturally occurring flavonol glucoside and has been reported to possess tremendous pharmacological potential ranging from neuroprotection to anticancer activity. However, the pharmacological role of icariin in esophageal cancer is still largely unclear. Here in the present study, icariin was evaluated for its anticancer activity against KYSE70 esophageal cancer cells and the possible underlying mechanism was determined. Icariin induced cytotoxicity with an IC50 of 40 mu M in esophageal cancer cells. These inhibitory effects were due to apoptosis through reactive oxygen species (ROS) mediated alterations in mitochondrial membrane potential (MMP). The results indicated that icariin enhanced the accretion of ROS upto 260% and reduced the MMP upto 48% at 100 mu M. Icariin also induced G2/M cell cycle arrest as evident from the significant increase in the G2 cell populations of KYSE70 esophageal cancer cells. Additionally, icariin inhibited esophageal cancer cell migration, invasion and metastasis by regulating the expression of epithelial to mesenchymal transition (EMT) markers. Results also indicated that icariin reduced cell viability and migration in part through suppression of the PI3K/AKT and STAT3 pathways. Taken together, our results indicate that icariin may prove a potential natural anticancer molecule against esophageal cancer.