摘要
背景:葫芦素-I通过抑制STAT3信号通路在多种恶性肿瘤中发挥强大的抗癌作用,但其在胃癌中是否同样具有抗癌作用及其作用机制,目前仍不清楚。目的:通过体外实验评估低浓度葫芦素-I对人胃癌细胞增殖、细胞周期和细胞凋亡的影响并初步探讨其可能作用机制。方法:以低浓度葫芦素-I处理人胃腺癌细胞株AGS和HGC-27,采用CCK-8试验和集落形成试验评估其对细胞增殖的抑制作用,流式细胞仪检测细胞周期和细胞凋亡,蛋白质印迹法检测细胞周期转换相关蛋白表达以及caspase-3/PARP细胞凋亡途径、STAT3、GADD45α和JNK/p38 MAPK信号通路激活情况。结果:低浓度葫芦素-I可在不抑制STAT3信号通路的情况下发挥强大的胃癌细胞生长抑制作用,此作用是通过诱导细胞周期G2/M期阻滞和细胞凋亡实现的。机制研究发现葫芦素-I可通过上调GADD45α和激活JNK/p38 MAPK信号通路诱导细胞凋亡,发挥抗胃癌作用。结论:本研究揭示了葫芦素-I抗胃癌作用的新机制,证明葫芦素-I是一个具有临床应用前景的化疗药物。
Background： Upon inhibition of STAT3 signaling pathway,cucurbitacin-I elicits anticancer effect in various malignancies. However,the anticancer effect and underlying mechanism of cucurbitacin-I in gastric cancer is still elusive.Aims： To explore the effect of low nanomolar cucurbitacin-I on cell proliferation,cell cycle and apoptosis in human gastric cancer cells and the underlying mechanism in vitro. Methods： Human gastric adenocarcinoma cell lines AGS and HGC-27 were treated with cucurbitacin-I at low nanomolar concentration. The anti-proliferative effect of cucurbitacin-I was detected by CCK-8 assay and colony formation assay. Flow cytometry was used to assess the cell cycle and apoptosis. Expressions of cell cycle-related proteins,as well as activation of related pathways such as caspase-3/PARP apoptotic pathway,STAT3,GADD45α and JNK/p38 MAPK signaling pathways were determined by Western blotting. Results： Cucurbitacin-I markedly inhibited the growth of gastric cancer cells at low nanomolar concentration by inducing G2/M phase arrest and apoptosis via a STAT3-independent manner. Furthermore,it was revealed that the anticancer effect of cucurbitacin-I was associated with up-regulation of GADD45α,activation of JNK/p38 MAPK signaling pathway and the subsequent apoptotic events. Conclusions： The present study provides new insights into the mechanism of anticancer effect of cucurbitacin-I,supporting cucurbitacin-I as an attractive therapeutic drug in gastric cancer.
出处
《胃肠病学》
2017年第9期523-528,共6页
Chinese Journal of Gastroenterology
