摘要
在细胞及动物个体水平探讨姜黄素类似物EF25-(GSH)2的抗肝癌作用。用不同浓度的EF25-(GSH)2处理体外培养的肝癌细胞、正常肝细胞以及HepG2荷瘤裸鼠,MTT法检测细胞存活率,电镜及激光共聚焦显微镜观察细胞形态,蛋白质免疫印迹法(Western blot)检测AMPK/Akt/mTOR相关通路蛋白磷酸化水平的变化。结果显示,EF25-(GSH)2对HepG2作用48 h的IC50为7.2μmol/L,对其生长抑制作用明显优于姜黄素及顺铂,且对正常细胞的杀伤作用较小。形态学观察到细胞中有自噬现象的发生。免疫印迹法结果提示,EF25-(GSH)2可能通过AMPK/Akt/mTOR的相关通路抑制肿瘤细胞生长。对肝癌模型裸鼠的实验显示,给药后的肿瘤体积明显缩小。该实验结果证明,EF25-(GSH)2具有良好的作为肝癌治疗药物的开发前景。
EF25-(GSH)2 is a curcumin analogue, and in this research we will study its anti-hepatoma effect in vitro and in vivo. Hepatoma cells, normal liver cells and HepG2 tumor-bearing nude mice were treated with different concentrations of EF25-(GSH)2. MTT assay was used to check cell viability, and cell morphology was observed with an electron microscope and confocal microscopy. Western blot was used to detect the changes in the phosphorylation level of AMPK/Akt/mTOR pathway related proteins. The results showed that the IC50 of EF25-(GSH)2 on HepG2 at 48 h was 7.2 μmol/L. EF25-(GSH)2 significantly inhibited the growth of HepG2 cells, the effect of which was much greater than those of curcumin and cisplatin, with slight toxicity to normal cells. Autophagy was observed with morphorlogical analysis. Western blot results indicated that EF25-(GSH)2 might inhibit tumor cell growth through AMPK/Akt/mTOR pathway. Liver cancer models in nude mice were established, and tumor volume was reduced after administration of EF25-(GSH)2. In vitro and in vivo results demonstrate that EF25-(GSH)2 has good prospects as a potential anti-hepatoma drug.
出处
《中国细胞生物学学报》
CAS
CSCD
北大核心
2014年第9期1241-1249,共9页
Chinese Journal of Cell Biology
基金
安徽省自然科学基金(批准号:KJ2012A030)
安徽省科技攻关项目(批准号:1301032140)资助的课题~~