目的探讨β-咔啉类生物碱对体外培养的人胃癌细胞株SGC-7901细胞的凋亡作用及PTEN、ERK m RNA表达的影响。方法体外培养人胃癌SGC-7901细胞,用CCK-8法测定不同浓度、不同时间β-咔啉类生物碱对胃癌细胞株的生长抑制率;用流式细胞技术检...目的探讨β-咔啉类生物碱对体外培养的人胃癌细胞株SGC-7901细胞的凋亡作用及PTEN、ERK m RNA表达的影响。方法体外培养人胃癌SGC-7901细胞,用CCK-8法测定不同浓度、不同时间β-咔啉类生物碱对胃癌细胞株的生长抑制率;用流式细胞技术检测细胞的凋亡;RT-PCR法检测PTEN、ERK m RNA表达的变化。结果β-咔啉类生物碱体外能抑制人胃癌细胞株SGC-7901细胞的增殖,促进了人胃癌SGC-7901细胞凋亡。不同浓度的对β-咔啉类生物碱作用于人胃癌SGC-7901细胞24、48 h后,PTEN m RNA的表达增高,ERK m RNA的表达减少,且呈剂量时间依赖性(P<0.05)。结论人胃癌SGC-7901细胞对β-咔啉类生物碱具有药物敏感性,β-咔啉类生物碱能诱导体外培养的胃癌细胞凋亡,其作用机制可能与β-咔啉类生物碱诱导胃癌细胞中PTEN-m RNA的表达增高和ERK m RNA的表达减少有关。展开更多
SMAD-4在肿瘤抑制方面有重要作用,但它在肿瘤发生中的作用及其与细胞周期进程中的一种关键调控因子——PTEN(phosphatase and tensin homolog deleted on chromosome 10)的关系仍存在争议.分别在人胚肾细胞(293T)及人胃癌细胞(MGC-803)...SMAD-4在肿瘤抑制方面有重要作用,但它在肿瘤发生中的作用及其与细胞周期进程中的一种关键调控因子——PTEN(phosphatase and tensin homolog deleted on chromosome 10)的关系仍存在争议.分别在人胚肾细胞(293T)及人胃癌细胞(MGC-803)中研究SMAD-4及TGF-β信号通路对PTEN基因表达的影响.结果发现,在293T细胞中,SMAD-4与TGF-β促进PTEN表达,而MGC-803细胞中,SMAD-4与TGF-β抑制PTEN转录.进一步研究发现,胃癌细胞中,SMAD-4与转化生长因子β(TGF-β)对PTEN的抑制可被PD98059(MEK抑制剂)解除.此外,SMAD-4的核转移也明显促进PTEN表达,并且PD98059存在下,SMAD-4与TGF-β协同刺激可促进胃癌细胞凋亡.综上,实验发现,SMAD-4作为一种co-Smad蛋白,通过TGF-β信号途径影响PTEN表达.展开更多
AIM:To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice.METHODS: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC ef...AIM:To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice.METHODS: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms of silibinin.RESULTS: Silibinin resulted in a potent dosedependent reduction of HuH7 xenografts in association with a significant decrease in Ki-67 and α-fetoprotein production, nuclear NF-κB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of HuH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI3K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of HuH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1.CONCLUSION: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression.展开更多
文摘目的探讨β-咔啉类生物碱对体外培养的人胃癌细胞株SGC-7901细胞的凋亡作用及PTEN、ERK m RNA表达的影响。方法体外培养人胃癌SGC-7901细胞,用CCK-8法测定不同浓度、不同时间β-咔啉类生物碱对胃癌细胞株的生长抑制率;用流式细胞技术检测细胞的凋亡;RT-PCR法检测PTEN、ERK m RNA表达的变化。结果β-咔啉类生物碱体外能抑制人胃癌细胞株SGC-7901细胞的增殖,促进了人胃癌SGC-7901细胞凋亡。不同浓度的对β-咔啉类生物碱作用于人胃癌SGC-7901细胞24、48 h后,PTEN m RNA的表达增高,ERK m RNA的表达减少,且呈剂量时间依赖性(P<0.05)。结论人胃癌SGC-7901细胞对β-咔啉类生物碱具有药物敏感性,β-咔啉类生物碱能诱导体外培养的胃癌细胞凋亡,其作用机制可能与β-咔啉类生物碱诱导胃癌细胞中PTEN-m RNA的表达增高和ERK m RNA的表达减少有关。
基金supported by grants from The National Natural Science Foundation of China(30971613,30671184)~~
文摘SMAD-4在肿瘤抑制方面有重要作用,但它在肿瘤发生中的作用及其与细胞周期进程中的一种关键调控因子——PTEN(phosphatase and tensin homolog deleted on chromosome 10)的关系仍存在争议.分别在人胚肾细胞(293T)及人胃癌细胞(MGC-803)中研究SMAD-4及TGF-β信号通路对PTEN基因表达的影响.结果发现,在293T细胞中,SMAD-4与TGF-β促进PTEN表达,而MGC-803细胞中,SMAD-4与TGF-β抑制PTEN转录.进一步研究发现,胃癌细胞中,SMAD-4与转化生长因子β(TGF-β)对PTEN的抑制可被PD98059(MEK抑制剂)解除.此外,SMAD-4的核转移也明显促进PTEN表达,并且PD98059存在下,SMAD-4与TGF-β协同刺激可促进胃癌细胞凋亡.综上,实验发现,SMAD-4作为一种co-Smad蛋白,通过TGF-β信号途径影响PTEN表达.
文摘AIM:To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice.METHODS: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms of silibinin.RESULTS: Silibinin resulted in a potent dosedependent reduction of HuH7 xenografts in association with a significant decrease in Ki-67 and α-fetoprotein production, nuclear NF-κB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of HuH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI3K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of HuH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1.CONCLUSION: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression.
