紫金牛三萜皂苷TSP02抑制人肝癌细胞增殖和侵袭作用机制研究  被引量:7

Study on inhibitory effect of triterpenoid saponin from Ardisia japonica TSP02 on proliferation and metastasis of human hepatocellular carcinoma cells and its mechanism

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作  者:赵晨阳[1] 惠林萍[1] 何琳[1] 李嵚[1] 

机构地区:[1]中国医科大学附属第四医院中心实验室,辽宁沈阳110032

出  处:《中国中药杂志》2013年第6期861-865,共5页China Journal of Chinese Materia Medica

基  金:辽宁省教育厅科学技术研究项目(L2010625)

摘  要:目的:研究紫金牛三萜皂苷类化合物TSP02体外诱导人肝癌细胞HepG2凋亡和侵袭迁移的作用及其分子机制。方法:采用MTT比色法,检测不同时间、不同浓度的TSP02对人肝癌HepG2细胞和人正常肝HL-7702细胞的增殖抑制作用。采用流式细胞术检测药物处理后HepG2和HL-7702细胞周期和凋亡变化情况。进一步用Western blot法检测TSP02对周期调控蛋白CDK1,2和4,细胞凋亡相关蛋白Caspase-8,以及细胞迁移侵袭相关蛋白TGF-β1和E-cadherin表达水平的影响。最后通过细胞划痕实验和Transwell小室体外侵袭实验检测HepG2细胞经过TSP02处理后迁移侵袭能力的变化。结果:TSP02显著抑制人肝癌细胞HepG2的生长,抑制效果有明显的时间依赖性和浓度依赖性,而对人正常肝细胞HL-7702的作用不明显。与对照组比较,TSP02处理24 h在造成HepG2细胞S期细胞消失,细胞凋亡率明显增加的同时,还能够显著降低HepG2细胞中CDK1,2,4的表达,提高促凋亡蛋白Caspase-8的表达和活化,而对正常肝HL-7702细胞无论在周期和凋亡率上均无明显影响。此外,TSP02处理后的HepG2细胞移动和侵袭性下降的同时,分别下调和上调了肝癌侵袭相关蛋白TGF-β1和E-cad-herin的表达。结论:TSP02选择性促进人肝癌细胞HepG2凋亡并抑制肝癌细胞的迁移和侵袭能力。TSP02的这些体外抗肿瘤活性与其改变周期和凋亡调控蛋白,并影响侵袭相关TGF-β1和E-cadherin的表达有关。Objective: To study the effect of TSP02, a triterpenoid saponin compound from Ardisia japonica, on proliferation and metastasis of in vitro induced human hepatoma HepG2 cells and its molecular mechanism. Method: MqT assay was performed to detect the inhibitory effect of TSP02 of different concentrations on proliferation of human hepatoma HepG2 and normal human hepatic cell HL-7702 cells. The changes in cell cycle and apoptotic of processed HepG2 and HL-7702 cells were detected by using flow cytometry. The effect of TSP02 on expression levels of CDK1, 2, 4, apoptosis-related protein Caspase-8, metastasis-related TGF-β1 and E-eadherin was measured by western blot. Wound-healing assay and transwell assay were performed to detect the changes in the metastasis of TSPO2-processed HepG2. Result: TSP02 significantly inhibited the proliferation of HepG2 cells, with notable time dependence and concentration dependence, but without remarkable effect on normal human liver HL-7702 cells. Compared with the control group, TSP02 processed for 24 h could eliminate HepG2 cells in S stage, significantly increase the cell apoptotic rate. Furthermore, TSP02 was capable of down-regulating the expression of multiple CDK1, 2, 4, and TGF-β1, and up-regulating the expression and activity of Caspase-8, without significant effect on cycle and apoptotic rate of normal human liver HL-7702 cells. Additionally, TSP02 caused metastasis and invasiveness HepG2 cells, while down-regulating liver cancer invasiveness-related TGF-β1 and E-cadherin. Conclusion: TSP02 selectively promotes apoptosis of liver cancer cell HepG2, and inhibits its metastasis and invasiveness. TSP02's in vitro antineo- plastic activity is related to the changes in cycle and apoptosis proteins, and the regulation in the expression of invasiveness-related TGF-βl and E-eadherin.

关 键 词:紫金牛三萜皂苷 肝癌 细胞周期 凋亡 侵袭 

分 类 号:R285[医药卫生—中药学] R735.7[医药卫生—中医学]

 

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