啤酒花中蛇麻酮诱导细胞凋亡及机制研究

Study on apoptosis effect induced by lupulone in Humulus Lupulus L. and its mechanism

通过体外抗肿瘤实验观察啤酒花(Humulus LupulusL.)中成分蛇麻酮(lupulone)对肿瘤细胞SGC-7901和HepG-2诱导细胞凋亡的作用,并揭示其作用机制.采用MTT法观察蛇麻酮体外抗肿瘤作用;采用流式细胞仪观察蛇麻酮对肿瘤细胞周期及细胞凋亡的影响;采用Fluo-3AM探针标记,激光共聚焦技术观测细胞内[Ca2+]i变化.蛇麻酮对肿瘤细胞SGC-7901及HepG-2均有较好的疗效.蛇麻酮作用于SGC-7901和HepG-2细胞48 h后,肿瘤细胞均有明显凋亡峰出现.蛇麻酮可以将肿瘤细胞SGC-7901和HepG-2的细胞周期阻滞在G0/G1和S细胞期,升高细胞凋亡指数(APO).蛇麻酮可使SGC-7901细胞内[Ca2+]i升高,使HepG-2细胞内[Ca2+]i先升高后降低.蛇麻酮通过诱导细胞凋亡来发挥抗肿瘤作用.蛇麻酮通过升高肿瘤细胞内[Ca2+]i启动肿瘤细胞凋亡机制,[Ca2+]i升高时Ca2+来源于细胞内钙库释放.

To investigate the pro-apoptosis effect of lupulone in Humulus Lupulus L. on two different kinds of tissue tumor SGC - 7901 and HepG - 2, and reveal its mechanism. MTT are adopted to study the antitumor activity of lupulone in vitro. Influences of lupulone on cell cycle and apoptosis are observed with flow cytometry （FCM）. LCM is adopted to measure [ Ca^2＋ ] i of the cells marked by Fluo - 3/AM probe. Lupulone had content antitumor activities to SGC -7901 and HepG -2. This paper observes the appearance of apoptosis peak after SGC -7901 and HepG -2 disposed by lupulone for 48 hours. Lupulone could blocks the cell cycle at G0/G1 and S phase, increase the apoptosis index（ APO% ）. Lupulone could increase [ Ca^2＋ ]i of SGC -7901, and [ Ca^2＋ ]i increasing with the dose＇s augment. [ Ca^2＋ ] i of HepG -2 increase first and decreased with the increase of lupulone dose. By inducing the apoptosis of tumor cells, lupulone had strong inhibitory action to both SGC -7901 and HepG-2. The possible mechanism is that lupulone could increase the Ca^2＋ in SGC -7901 and HepG - 2, this kind of rises of Ca^2＋ is from the release of cellular storage.