乙酰基-11-酮基-β-乳香酸通过对Wnt/β-catenin信号的调控机制抑制人胃癌细胞生长作用研究

被引：0

作者：

谢纪珍

机构：

[1] 山东大学

关键词：

胃癌; 乙酰基-11-酮基-β-乳香酸(AKBA); Wnt/β-catenin信号通路; 凋亡; SGC-7901移植瘤裸鼠;

D O I：

暂无

年度学位：

2012

学位类型：

硕士

导师：

曲显俊;

摘要：

乙酰基-11-酮基-β-乳香酸(AKBA)是一种乳香酸的衍生物,乳香酸是齿叶乳香树树胶脂中的有效成分。AKBA己被证实对于一些慢性炎症和癌症有很好的治疗效果,此研究中,我们在体内和体外评价了AKBA对人胃癌生长的影响。对于体外,通过CCK-8和克隆形成实验检测了AKBA对癌细胞的生长抑制情况。种植了SGC-7901癌细胞的移植瘤裸鼠用于评价AKBA在体内的治疗效果。口服AKBA显著延缓了移植瘤的生长,而对裸鼠体重则无明显影响。AKBA对SGC-7901癌细胞的生长抑制可能是因为其可以诱导细胞凋亡,表现为细胞形态上出现凋亡的特征,Annexin-V/FITC和PI染色的细胞数增加,以及DNA梯状条带的出现等。裸鼠SGC-7901移植瘤中同样观察到AKBA的促凋亡效果,表现为TUNEL染色的细胞数增加。AKBA处理的SGC-7901癌细胞中,蛋白质印迹检测到激活型caspase-9, caspase-3以及PARP增加,Bax/Bal-2比率增加。进一步研究表明AKBA不仅可抑制Wnt/β-catenin(连环蛋白)信号通路中的重要信号分子(3-catenin和GSK3β的表达,并且还可以抑制其靶蛋白,包括细胞周期素D1(cyclin D1)、PCNA、生存素(survivin)、c-Myc、基质金属蛋白酶-2和-7(MMP-2和-7)的表达。以上结果证明AKBA是通过下调Wnt/p-catenin信号通路抑制胃癌生长和诱导胃癌细胞凋亡的。AKBA有望成为治疗胃癌的辅助药物。

引用

页数：61

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