龙葵碱对胰腺癌细胞裸鼠移植瘤的抑制作用及机制研究

inhibitory effect of Solanine on apoptosis of human pancreatic cancer implanted on nude mice and its mechanism

目的探讨龙葵碱对胰腺癌细胞SW1990裸鼠移植瘤的抑制作用并初步研究其作用机制。方法建立胰腺癌细胞SW1990的裸鼠荷瘤模型,随机分为对照组和实验组,每组10只。肿瘤接种成功第2周起对照组和实验组分别腹腔注射溶媒(含1‰二甲亚砜)1 mL、龙葵碱10 mg/kg,隔天给药1次,共给药2周。每次给药结束用游标卡尺记录肿瘤大小。给药结束后颈椎脱臼处死裸鼠,测量瘤体重量并计算抑瘤率,留取新鲜肿瘤组织用RT-PCR和免疫组化检测Bcl-2、Bax和Caspase-3基因mRNA和蛋白表达情况。结果与对照组相比,实验组裸鼠肿瘤生长受到显著抑制(P<0.05),实验组的肿瘤组织Bcl-2表达阳性率明显降低(实验组90%vs对照组46%,P<0.01),Bax(实验组38%vs对照组70%,P<0.01)和Caspase-3(实验组22%vs对照组74%,P<0.01)的表达阳性率明显升高。结论龙葵碱在裸鼠体内能显著抑制人胰腺癌细胞SW1990的增殖,此抑制作用呈明显的时间依赖性。龙葵碱发挥上述作用的机制可能在于诱导胰腺癌细胞凋亡。

objective To investigate the inhibitory effect and mechanism of Solanine on human pancreatic cancer cells SW1990 implanted on nude mice. Methods Pancreatic cancer cells SW1990 which were in the state of logarithmic phase were implanted on nude mice. After two weeks of the implantation, the nude mice were randomized into two groups（n=10）： control group, 1‰ dimethylsulfoxide（DMSO） 1 m L was injected into the abdominal cavity, once every other day; test group, Solanine at dose of 10 mg/kg was injected into the abdominal cavity, once every other day. All treatment lasted for two weeks. After the treatment, the nude mice were killed and then the tumor weight and the inhibition rate were determined; the m RNA expression of Bcl-2, Bax and Caspase-3 were analyzed with RT-PCR and the protein expression were analyzed with immunohistochemistry. Results Compared with the control group, the tumor growth of the nude mice in the test group was significantly inhibited（P〈0.05）. The results of RT-PCR and immunohistochemistry test showed that Solanine increased the expression of Caspase-3 and Bax, at the same time, inhibited the Bcl-2（all P〈0.01）. Conclusion Solanine can significantly inhibit the proliferation of pancreatic cancer cells SW1990 in nude mice in a time-dependent manner. Furthermore, the inhibitory effect of solanine may be achieved by the apoptosis induction in pancreatic cancer.