阿魏酸抑制A549肺癌移植瘤生长及其机制研究

Ferulic acid inhibits lung cancer growth and its mechanism

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;q RT-PCR检测移植瘤组织中哺乳动物雷帕霉素靶蛋白(m TOR)的mRNA表达水平,Western blot法和免疫组化法检测移植瘤组织中m TOR、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m TOR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m TOR表达,抑制Ki-67蛋白表达和促进Caspase-3蛋白表达有关。

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 25 mg/L, ferulic acid 50 mg/L or ferulic acid 100 mg/L. The tumor inhibition rate was calculated; the mRNA and protein expression of m TOR in xenografts was detected with q RT-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 100 mg/L） was inhibited, with tumor inhibition rates of 32.82%, 43.75% and 62.51%,respectively. Compared with control group, the expression of m TOR 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 m TOR expression, inhibiting Ki-67 expression and promoting Caspase-3 expression.