维泰醇对人骨肉瘤移植荷瘤裸鼠肿瘤生长的抑制作用及对Akt/GSK3信号通路的影响  

Inhibitory Effect of Alternol on the Tumor Growth in Human Osteosarcoma Xenografted Nude Mice and Its Effect on Akt/GSK3 Signaling Pathway

作　　者：王碧涛 周前[1] 刘武[1] 潘璇璇[2] Wang Bitao;Zhou Qian;Liu Wu;Pan Xuanxuan(Department of Orthopaedics,Boai Hospital of Taizhou City,Zhejiang Taizhou 318050,China;Department of Orthopaedics,the Second Affiliated Hospital of Wenzhou Medical University)

机构地区：[1]台州市博爱医院骨科,浙江台州318050 [2]温州医科大学附属第二医院骨科

出　　处：《中国药师》2021年第2期252-255,260,共5页China Pharmacist

摘　　要：目的:探讨维泰醇对人骨肉瘤移植荷瘤裸鼠肿瘤生长的抑制作用及对丝苏氨酸蛋白激酶(Akt)/糖原合酶激酶3(GSK3)信号通路的影响。方法:将30只BALB/c-nu品系裸鼠分为3组:正常对照组、环磷酰胺组(25 mg·kg^(-1))和维泰醇组(150 mg·kg^(-1)),每组10只。用培养的U-2OS细胞注射到裸鼠右胫骨骨髓腔内制备U-2OS荷瘤裸鼠模型,造模成功后环磷酰胺组和维泰醇组灌胃给予相应药物,正常对照组给予等量生理盐水,1次/d,给药周期为4周。末次给药次日,处死裸鼠,完整剥离出原位瘤块,计算抑瘤率,检测瘤块组织中相关蛋白表达水平及细胞凋亡情况。结果:与正常对照组比较,环磷酰胺组和维泰醇组瘤块重量、N-钙黏蛋白(N-cadherin)、波形蛋白(vimentin)、纤维连接蛋白(fibronectin)、p-Akt、磷酸化糖原合酶激酶3(p-GSK3)和锌指转录因子(Snail)蛋白表达水平降低,抑瘤率、上皮细胞钙黏蛋白(E-cadherin)蛋白表达水平和细胞凋亡率增加(P<0.05);与环磷酰胺组比较,维泰醇组瘤块重量、N-cadherin、vimentin、fibronectin、p-Akt、p-GSK3和Snail蛋白表达水平增加,抑瘤率、E-cadherin蛋白表达水平和细胞凋亡率降低(P<0.05);各组Akt和GSK3蛋白表达水平差异无统计学意义(P>0.05)。结论:维泰醇可能通过Akt/GSK3信号通路抑制上皮-间质转化(EMT)并降低骨肉瘤细胞的侵袭能力,促进骨肉瘤细胞凋亡。Objective: To investigate the inhibitory effect of alternol on the tumor growth in human osteosarcoma xenografted nude mice and the effect on serine-threonine kinase(Akt)/glycogensynthasekinase3(GSK3) signaling pathway. Methods: Thirty nude mice of BALB/c-nu strain were divided into three groups: normal control group,cyclophosphamide group(25 mg·kg^(-1)) and alternol alcohol group(150 mg·kg^(-1)) with 10 ones in each group. The nude mice bearing U-2OS tumors were made by injecting cultured U-2OS cells into the bone marrow cavity of the right tibia of nude mice. After the successful modeling,cyclophosphamide group and alternol alcohol group were given corresponding drug by gavage,while the normal control group was given the same amount of saline,once a day. The drug treatment course was 4 weeks. The next day after the last administration,nude mice were executed,and the tumors in situ were removed completely. The inhibition rate was counted,and the expressions of related proteins and the apoptosis of tumors were detected. Results: Compared with those in the normal control group,the tumor mass weight,expression levels of N-cadherin,vimentin,fibronectin,p-Akt,phosphorylation glycogensynthasekinase3(p-GSK3) and Snail protein in cyclophosphamide group and alternol group were significantly decreased,while the inhibition rate,E-cadherin protein expression and apoptotic rate significantly increased(P<0.05). Compared with those in cyclophosphamide group,the weight of tumor mass,N-cadherin,Vimentin,fibronectin,p-Akt p-GSK3 and Snail protein in alternol group were increased,while the inhibition rate,expression of E-cadherin protein and apoptosis rate significantly decreased(P<0.05). The expression levels of Akt and GSK3 protein in each group had no significant differences(P>0.05). Conclusion: Alternol can inhibit epithelial-mesenchymal transition(EMT) through Akt/GSK3 signaling pathway,and reduce the invasive ability of osteosarcoma cells and promote the apoptosis of osteosarcoma cells.

关 键 词：维泰醇 骨肉瘤 丝苏氨酸蛋白激酶/糖原合酶激酶3信号通路 抑制作用 

分 类 号：R965.1[医药卫生—药理学]