白桦脂醇通过抑制PI3K/AKT途径抑制宫颈癌小鼠移植瘤增殖

目的:阐明白桦脂醇对宫颈癌细胞系c4-1移植瘤模型裸鼠的影响和机制。方法:皮下注射宫颈癌细胞系c4-1建立异种移植瘤模型,将移植瘤BALB/c裸鼠模型随机分为3组:对照组(DMSO)、白桦脂醇低剂量组(Betulin50)、白桦脂醇高剂量组(Betulin200),进行后续使用。白桦脂醇治疗后,检测移植瘤体积和裸鼠存活率;免疫组化检测Ki67和血管内皮生长因子(VEGF)表达水平;TUNEL实验检测移植瘤细胞凋亡情况;Westernblot检测磷脂酰肌醇3-激酶(PI3K)/AKT通路蛋白表达情况和磷酸化情况。结果:与对照组(DMSO)相比较,白桦脂醇低剂量组(Betulin50)、白桦脂醇高剂量组(Betulin200)肿瘤体积明显减小(P<0.01),裸鼠存活率明显增加(P<0.01),Ki67和VEGF表达水平明显下降(P<0.01),且PI3K/AKT磷酸化水平明显被抑制(P<0.01)。结论:白桦脂醇能抑制c4-1移植瘤体积,增加移植瘤裸鼠存活率,下调Ki67和VEGF表达水平和PI3K/AKT磷酸化水平。白桦脂醇可能通过抑制PI3K/AKT信号通路抑制宫颈癌细胞系c4-1移植瘤。

Betulin on inhibition of PI3K/AKT activity and on survival rate in cervical cancer cell line c4-1 xenograft tumor

Objective: To elucidate the effects and mechanisms of betulin on xenograft tumor model of cervical cancer cell line c4-1. Methods: Xenograft tumor model was set up with subcutaneous injection of cervical cancer cell line c4-1,the BALB/c nude mice xenograft tumor model were randomly divided into 3 groups:control group (DMSO),betulin low dose group (Betulin 50),betulin high dose group (Betulin 200) for subsequent experiments.After the treatment of betulin,the tumor volume and survival rate were detected.Expression levels of Ki67 and vascular endothelial growth factor(VEGF) were detected by immunohistochemical detection.TUNEL was used to test the apoptosis of xenograft tumor.Western blot was used to detect the relative expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT pathway protein. Results: Compared with control group (DMSO),the tumor volume of betulin low dose group (Betulin 50) and betulin high dose group (Betulin 200) were obviously decreased ( P <0.01).The survival rate of mice was increased significantly ( P <0.01).Additionally,the expression level of Ki67 and VEGF were decreased obviously ( P <0.01).Moreover,PI3K/AKT phosphorylation levels were significantly inhibited ( P <0.01). Conclusion: Betulin can inhibit the tumor volume of c4-1 by dose-dependent inhibition,increase the survival rate of transplanted tumor mice,and down-regulate the expression level of Ki67 and VEGF and the level of PI3K/AKT phosphorylation.Betulin may inhibit the cervical cancer cell line c4-1 transplanted tumor by inhibiting the PI3K/AKT signaling pathway.