摘要
目的:探讨大黄素及联合阿帕替尼对人甲状腺癌细胞K1的抑制作用及其机制。方法:细胞分组:空白组(PBS)、大黄素组(100μmol/L)、阿帕替尼组(10μmol/L)、联合组(100μmol/L大黄素+10μmol/L阿帕替尼),不同给药时间后,CCK-8法检测细胞增殖活性,划痕实验和Transwell法检测细胞迁移和侵袭能力,流式细胞仪检测细胞凋亡率,Western blotting检测Bax(促凋亡蛋白)、Bcl-2(抗凋亡蛋白)、Caspase-3(半胱氨酸蛋白酶-3)及VEGFR-2(血管内皮生长因子受体-2)蛋白表达。建立人甲状腺癌细胞K1裸鼠移植模型,分为模型组、大黄素组(10 mg/kg)、阿帕替尼组(100 mg/kg)、联合组(10 mg/kg大黄素+100 mg/kg阿帕替尼),分组给药,每日2次,连续给药28 d,观察对肿瘤生长的影响。结果:大黄素组、阿帕替尼组和联合组的细胞存活率、凋亡率、细胞迁移和侵袭个数及Bcl-2及VEGFR-2蛋白表达均低于空白组,大黄素组、阿帕替尼组和联合组的Bax、Caspase-3表达均高于空白组;均有统计学差异(P<0.05,P<0.01)。大黄素组、阿帕替尼组和联合组对瘤体的抑制率均显著高于模型组,均有统计学差异(P<0.05,P<0.01)。联合组上述变化最为显著。结论:大黄素和阿帕替尼对人甲状腺癌细胞K1细胞的生长均具有明显的抑制作用,大黄素联合阿帕替尼后效果更为显著,可能与调节Bax/Bcl-2平衡,激活Caspase-3表达和抑制VEGFR-2的表达并诱导凋亡有关。
Objective:To investigate the inhibitory effects of Emodin and its combination with Apatinib on Human Thyroid Cancer Cell K1 and its mechanism.Methods:Human thyroid cancercell K1 was divide into groups as blank group(PBS),Emodin group(100μmol/L),Apatinib group(10μmol/L),combination group(100μmol/L emodin+10μmol/L Apatinib).After cultured for different time,CCK-8 method was used to detect cell proliferation activity.Scarification assay and Transwell method were used to detect capability of cell migration and invasion.Flow cytometry was used to detect apoptosis rate of cell K1.Western blotting was used to detect the expressions of Bax,Bcl-2,Caspase-3 and VEGFR-2 protein.Establishing transplantation tumor model of nude mice with Human Thyroid Cancer Cell K1,divided into model group,Emodin group(10 mg/kg),Apatinib group(100 mg/kg),combination group(10 mg/kg Emodin+100 mg/kg Apatinib),twice a day for 28 days,to observe the effect on tumor growth.Results:The cell survival rate,apoptosis rate,cell migration and invasion number,the expressions of Bcl-2 and VEGFR-2 in the Emodin group,Apatinib group and combination group were lower than those in the blank group.The Bax,Caspase-3 expressions and the inhibition rate of tumor in the Emodin group,Apatinib group and combination group were significantly higher than those of blank group(P<0.05,P<0.01).The Tumor inhibition rate of Emodin group,Apatinib group and combination group were significantly higher than those of model group(P<0.05,P<0.01).The effects of combination group were the best.Conclusion:Emodin and Apatinib both can significantly inhibit the proliferation of Thyroid Cancer Cell K1,and the effect was more obvious in combination group,that may be related to regulating the balance of Bax/Bcl-2,activating the expression of Caspase-3 and inhibiting the expression of VEGFR-2,reducing its activity and inducing apoptosis.
作者
张维
彭友
滕尧树
ZHANG Wei;PENG You;TENG Yaoshu(Hangzhou First People’s Hospital Affiliated with Medical College of Zhejiang University,Hangzhou,Zhejiang 310006)
出处
《中国中医药科技》
CAS
2021年第5期733-738,共6页
Chinese Journal of Traditional Medical Science and Technology
基金
浙江省杭州市卫生计生科技计划项目(A20200274)。
