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Effect of borrelidin on hepatocellular carcinoma cells in vitro and in vivo

机译:硼瑞林对肝癌细胞 体内的影响

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high prevalence and mortality. Borrelidin, produced by several actinomycete bacteria of Streptomycin sp. exhibited diversiform activities including anti-bacterial, anti-viral, anti-angiogenic, and anti-tumor. However, the effect of borrelidin on HCC cells has not been characterized. The present study demonstrated borrelidin exhibited great potential to inhibit the growth of HCC cells, HepG2 and SMMC7721 in vitro. Western blot and real-time qPCR analysis revealed that borrelidin decreased the expressions of cyclin D1, cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and increased the expression of p21, thereby inducing G0/G1 cell cycle arrest. Moreover, borrelidin down-regulated expression of Bcl-2, up-regulated expression of Bax and increased cleavages of caspase-9 and caspase-3 to activate caspase-dependent apoptosis in HCC cells. Borrelidin inhibited migration and invasion through suppressing the expression of MMP-2 and MMP-9 in HCC cells. Further investigation indicated that the anti-tumor effect of borrelidin was mediated by MAPKs signaling pathway. In addition, an in vivo experiment revealed that borrelidin suppressed tumor growth in SMMC7721 xenograft model mice with few side effects. Cell cycle arrest and induced apoptosis were also observed in tumor tissues of model mice treated with borrelidin.
机译:肝细胞癌(HCC)是最常见的肝癌,其患病率和死亡率很高。硼瑞林,由链霉素的几种放线菌细菌产生。表现出多种形式的活性,包括抗菌,抗病毒,抗血管生成和抗肿瘤。但是,尚未确定硼瑞林对HCC细胞的作用。本研究表明硼瑞林具有抑制HCC细胞,HepG2和SMMC7721体外生长的巨大潜力。 Western印迹和实时qPCR分析表明,硼瑞林降低了cyclin D1,cyclin D3,cyclin E1,CDK2,CDK4和CDK6的表达,并增加了p21的表达,从而诱导了G0 / G1细胞周期停滞。此外,borrelidin下调Bcl-2的表达,上调Bax的表达并增加caspase-9和caspase-3的裂解,从而激活HCC细胞中caspase依赖性凋亡。硼瑞林通过抑制HCC细胞中MMP-2和MMP-9的表达来抑制迁移和侵袭。进一步的研究表明,硼瑞林的抗肿瘤作用是由MAPKs信号通路介导的。此外,一项体内实验表明,硼瑞林抑制了SMMC7721异种移植模型小鼠的肿瘤生长,且几乎没有副作用。在用硼瑞林治疗的模型小鼠的肿瘤组织中也观察到细胞周期停滞和诱导的凋亡。

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