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基于RhoA/ROCK信号通路番茄红素对骨肉瘤MG63细胞荷瘤小鼠的抑瘤作用机制研究 被引量:1

Lycopene act as antitumor on osteosarcoma MG63 cells xenograft mice by RhoA/ROCK signaling pathway
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摘要 目的探讨番茄红素(LP)对人骨肉瘤MG63细胞增殖及荷瘤裸鼠肿瘤抑制作用和其潜在机制。方法选取对数生长期的人骨肉瘤MG63细胞,根据实验目的分为5组:对照组、LP 5、10和20μg/mL组和顺铂(DDP,40μg/mL)组;LP或DDP处理细胞48 h后,MTT检测细胞抑制率、流式细胞术检测细胞周期和细胞凋亡的改变。背部皮下注射MG63细胞建立荷瘤裸鼠模型,设为模型组、LP 10、20、40 mg·kg^(-1)·d^(-1)组和DDP(2 mg/kg)组,每组10只;接种后使用LP或DDP处理14 d后处死裸鼠,称量瘤体质量并计算抑瘤率,Western blot检测肿瘤组织中小GTPase RhoA/Rho相关卷曲螺旋形成的蛋白激酶(ROCK)信号通路相关蛋白的表达水平。结果在体外试验中,与对照组比较,LP 5、10、20μg/mL组和DDP组细胞增殖抑制率明显升高、细胞周期G_(0)/G_(1)期明显延长,细胞凋亡率明显升高,差异有统计学意义(P<0.05)。在体内试验中,LP 20、40 mg·kg^(-1)·d^(-1)组瘤质量较模型组明显减轻、抑瘤率明显升高,肿瘤组织RhoA和ROCK蛋白表达水平下调,差异有统计学意义(P<0.05)。结论LP阻碍了MG63的生长,可能与抑制RhoA/ROCK信号通路有关。 Objective To explore the inhibitory role of lycopene(LP)on the proliferation of human osteosarcoma cells MG63 cells of xenograft mice and its potential mechanism.Methods Human osteosarcoma MG63 cells at logarithmic growth phase were selected divided into five groups according to experimental purpose:control group,LP(5,10 and 20μg/mL)group and cisplatin(DDP,40μg/mL)group.Cells were treated with LP or DDP for 48 h,MTT was used to detect the cell inhibition,and flow cytometry was used to detect the changes in cell cycle and apoptosis.MG63 cells were injected subcutaneously into the back to establish a xenograft model,and these animals were set as model group,LP group(10,20 and 40 mg·kg^(-1)·d^(-1))and DDP group(2 mg/kg),with the number of 10 in each group.After inoculation,nude mice were treated with LP or DDP for 14 days and sacrificed later.The tissues were weighed and the tumor inhibition rates were calculated.The expression levels of small GTPase RhoA/Rho associated coiled-coil containing protein kinase(ROCK)signal pathway related proteins in tumor tissues were detected by Western blot.Results In vitro experiments,compared with the control group,it was clear to see that the rate of proliferation inhibition was increased significantly in LP(5,10,and 20μg/mL)group and DDP group,cell cycle G 0/G 1 phase was prolonged significantly and cell apoptosis rate was increased significantl y.The above statistical results have statistical difference(P<0.05).In vivo experiments,the tumor mass in the LP 20 and 40 mg·kg^(-1)·d^(-1) group was reduced significantly,the tumor inhibition rate was increased significantly,the proteins levels of RhoA and ROCK in tumor tissue were down-regulated,the differences were statistically significant(P<0.05).Conclusion LP hinders the growth of MG63,which may be related to the inhibition of RhoA/ROCK signaling pathway.
作者 王新强 吴良邦 章月红 顾增辉 WANG Xinqiang;WU Liangbang;ZHANG Yuehong;GU Zenghui(The Third Department of Orthopedics,903 Hospital,Joint Logistics Support Force of Chinese People’s Liberation Army,Hangzhou,Zhejiang 310004,China)
出处 《重庆医学》 CAS 2022年第18期3069-3073,共5页 Chongqing medicine
基金 浙江省医药卫生科技计划项目(2019329727)。
关键词 番茄红素 骨肉瘤 MG63细胞 细胞增殖 细胞周期 细胞凋亡 RhoA/ROCK信号通路 lycopene osteosarcoma MG63 cells cell proliferation cell cycle apoptosis RhoA/ROCK signaling pathway
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