黄芩苷对CA46细胞裸鼠异种移植瘤的作用及机制

目的: 研究黄芩苷抗CA46细胞裸鼠异种移植瘤的作用并探讨其机制。方法: 构建CA46细胞裸鼠异种移植瘤模型,将荷瘤裸鼠随机分为5组:阴性对照组、15 mg/kg黄芩苷组、30 mg/kg黄芩苷组、60 mg/kg黄芩苷组和4 mg/kg依托泊甙 (VP-16) 阳性对照组。采用腹腔注射方式给药,12 d后处死部分裸鼠,对剥取的瘤块称重计算抑瘤率,并进行透射电镜、病理学和Western blotting检测;观察各组未处死的裸鼠直至全部死亡,研究黄芩苷对荷瘤裸鼠生存时间的影响。结果: 黄芩苷明显抑制了CA46细胞裸鼠异种移植瘤的生长,引起肿瘤细胞的凋亡、坏死以及p-Akt、NF-κB、mTOR和p-mTOR蛋白表达的下调;随着黄芩苷剂量的增加,黄芩苷治疗组荷瘤裸鼠的生存时间明显延长。结论: 黄芩苷可抑制CA46细胞裸鼠异种移植瘤的生长,诱导肿瘤细胞的凋亡,并延长荷瘤裸鼠的生存时间,其机制可能与下调PI3K/Akt/NF-κB和PI3K/Akt/mTOR信号通路有关。

Effects of baicalin on CA46 cell xenografts in nude mice

AIM: To study the effects of baicalin on CA46 cell xenografts in nude mice.METHODS: The nude mice with CA46 cell xenografts were treated with drugs via intraperitoneal injection daily,and were divided into 5 groups: negative control group,15 mg/kg baicalin group,30 mg/kg baicalin group,60 mg/kg baicalin group and 4 mg/kg etoposide(VP-16) positive control group.After 12-day treatment,the weight of CA46 cell xenografts stripped from some nude mice in the 5 groups was used to evaluate the effect of baicalin on xenograft growth in the nude mice.The apoptosis,necrosis and pathological changes of the xenograft cells were examined under light microscope and transmission electronic microscope respectively.The expression levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway-related proteins extracted from xenografts were determined by Western blotting.The other nude mice with CA46 cell xenografts in the 5 groups continued to be treated with the drugs until death in order to evaluate the effect of balcalin on survival time of the nude mice with CA46 cell xenografts.RESULTS: Baicalin remarkably inhibited the growth of CA46 cell xenografts,induced apoptosis and necrosis of xenograft cells,and reduced the protein expression of phospho-Akt(p-Akt),nuclear factor-kappa B(NF-κB),mammalian target of rapamycin(mTOR) and phospho-mTOR(p-mTOR) in the xenografts after 12-day treatment.Furthermore,baicalin prolonged the survival time of the nude mice with CA46 cell xenografts in a dose-dependent manner.CONCLUSION: Baicalin inhibits the growth and induces apoptosis of CA46 cell xenografts in the nude mice,and prolongs the survival time of the nude mice with CA46 cell xenografts through the mechanism of down-regulating PI3K/Akt/NF-κB and PI3K/Akt/ mTOR signaling pathways.