摘要
目的 探究甘草查尔酮A(licochalcone A,LCA)对骨肉瘤细胞增殖和凋亡的影响及相关分子机制。方法 体外培养骨肉瘤HOS和U2OS细胞,通过MTT实验检测不同浓度LCA处理不同时间对HOS和U2OS细胞增殖的影响;加入终浓度分别为对照组(含0.1%DMSO的培养液)、5、10及20μmol·L^(-1)的LCA处理细胞48 h,流式细胞术检测LCA对HOS和U2OS细胞凋亡的影响,通过Western blot检测LCA对细胞凋亡相关蛋白cleaved PARP1、Bcl-2、Bax以及Akt和ERK蛋白表达水平的影响;通过裸鼠荷瘤实验从体内水平探究LCA的抗肿瘤作用。结果 MTT实验结果表明,LCA可抑制骨肉瘤HOS和U2OS细胞的增殖,并且呈时间和剂量依赖性;流式细胞术的结果表明,LCA可引起细胞凋亡。Western blot结果显示,ERK和Akt的磷酸化被抑制,cleaved PARP1和Bax的表达量升高,Bcl-2的表达量降低。裸鼠荷瘤实验表明,注射LCA后肿瘤体积明显减小(P<0.05),肿瘤的质量明显减小(P<0.01)。结论 LCA可以抑制骨肉瘤细胞的增殖并诱导凋亡,其作用机制可能与抑制Akt/ERK信号通路有关。
Aim To investigate the effect of licochalcone A(LCA)on proliferation and apoptosis of osteosarcoma HOS and U2OS cells and to explore its possible molecular mechanism.Methods The HOS and U2OS cells were cultured in vitro.MTT assay was used to detect the proliferation of the cells after being treated with different concentrations of LCA at different intervention time.Then HOS and U2OS cells were treated with 0.1%DMSO,or different concentrations of LCA(5,10,20μmol/L),and flow cytometry was used to assess the cell apoptosis.The expression of apoptosis-related protein cleaved PARP1,Bcl-2,Bax,and Akt,ERK were detected by Western blot.The antitumor effect of LCA was detected on U2OS xenograft mice in vivo.Results LCA could inhibit the proliferation of HOS and U2OS cells in a time-and dose-dependent manner.Flow cytometry showed that LCA treatment could induce cell apoptosis.Western blot results showed that LCA could inhibit the phosphorylation of Akt and ERK,increase the expression of cleaved PARP1 and Bax,and decrease the expression of Bcl-2.In the tumor-bearing mouse models,LCA significantly decreased the tumor volume(P<0.05)and weight(P<0.01).Conclusions LCA could inhibit the proliferation of HOS and U2OS and induce apoptosis possibly by inhibiting the Akt/ERK signaling pathway.
作者
范晓丽
王梨明
FAN Xiao-li;WANG Li-ming(College of Pharmacy,Guilin Medical University,Guilin Guangxi 541100,China;College of Clinical Medicine,Guilin Medical University,Guilin Guangxi 541001,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第4期653-658,共6页
Chinese Pharmacological Bulletin
基金
广西省教育厅中青年能力提升项目(No 2019KY0541)。
关键词
甘草查尔酮A
骨肉瘤
细胞增殖
细胞凋亡
Akt/ERK信号通路
裸鼠成瘤
licochalcone A(LCA)
osteosarcoma
cell proliferation
cell apoptosis
Akt/ERK signaling pathway
tumor formation in nudemice