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阿魏酸抑制A549肺癌移植瘤生长及其机制研究
吴竞1, 王廷祥, 魏楠, 吴秀绍, 刘杏娥
浙江医院肿瘤科
摘要:
目的探究阿魏酸对A549裸鼠肺癌移植瘤的抑制作用及其可能机制。方法将40只构建成功的肺癌移植瘤BALB/c裸鼠采用随机数字表法分为模型对照组、阿魏酸25mg/L组、阿魏酸50mg/L组和阿魏酸100mg/L组4组,每组10只,通过腹腔注射给药。通过计算肿瘤的瘤体积,称重瘤体质量,计算各组抑瘤率;qRT-PCR检测移植瘤组织中哺乳动物雷帕霉素靶蛋白(mTOR)的mRNA表达水平,Westernblot法和免疫组化法检测移植瘤组织中mTOR、增殖蛋白Ki-67和凋亡蛋白半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的蛋白表达水平。结果与模型对照组相比,不同剂量的阿魏酸(25、50和100mg/L)组裸鼠的移植瘤组织生长受到抑制,抑瘤率分别为32.82%、43.75%和62.51%。与模型对照组相比,不同剂量的阿魏酸组mTOR的mRNA和蛋白表达水平均下降(均P<0.05),Ki-67蛋白表达水平均下降(均P<0.05),Caspase-3蛋白表达水平均升高(均P<0.05)。结论阿魏酸对A549肺癌移植瘤生长具有显著抑制作用,可能与下调mTOR表达,抑制Ki-67蛋白表达和促进Caspase-3蛋白表达有关。
关键词:  阿魏酸 mTOR 肺癌 移植瘤
DOI:10.12056/j.issn.1006-2785.2018.40.12.2017-2134
分类号:
基金项目:
Ferulic acid inhibits lung cancer growth and its mechanism
Abstract:
Objective To investigate the inhibitory effect of ferulic acid on A549 xenografts in nude mice and its mechanisms. Methods BALB/c nude mice were xenografted with human lung cancer A549. Forty tumor-bearing nude mice were assigned to receive intraperitoneal injection of normal saline(control group), ferulic acid 25mg/L, ferulic acid 50mg/L or ferulic acid 100mg/L. The tumor inhibition rate was calculated; the mRNA and protein expression of mTOR in xenografts was detected with qRT-PCR, Western blot and immunohistochemistry, respectively; the protein expression of Ki-67 and Caspase-3 was detected by Western blot and immunohistochemistry. Results Compared with the control group, the growth of transplanted tumor in ferulic acid treated groups(25, 50 and 100mg/L) was inhibited, with tumor inhibition rates of 32.82%, 43.75% and 62.51%, respectively. Compared with control group, the expression of mTOR mRNA and protein in the transplanted tumor tissues of the ferulic acid treatment groups was decreased(all P<0.05). The expression of Ki-67 in tumor tissue decreased and the expression of Caspase-3 increased(all P<0.05). Conclusion Ferulic acid significantly inhibits the growth of A549 lung cancer xenografts in nude mice, which may be related to the down-regulating mTOR expression, inhibiting Ki-67 expression and promoting Caspase-3 expression.
Key words:  Ferulic acid mTOR Lung cancer Xenografts