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该文旨在研究人肝细胞癌异位移植瘤裸鼠模型中沉默信息调节因子3(silent information regulator 3,SIRT3)对肝细胞癌生长的影响及其机制。建立稳定过表达SIRT3和pc DNA3.1的SK-Hep-1细胞株;将稳定过表达SIRT3和pc DNA3.1的细胞悬液分别注射入裸鼠皮下,实时监测两组移植瘤的生长,25 d后剥离出移植瘤并称重;免疫组织化学检测移植瘤中SIRT3、Ki67的表达水平;应用定量逆转录PCR(q RT-PCR)筛选SIRT3影响移植瘤生长的下游靶向分子,Western blot检测下游靶向分子Bax的表达量以及移植瘤中cleaved-PARP(poly ADP-ribose polymerase)的表达水平。结果显示,过表达SIRT3组移植瘤的体积和重量都小于pc DNA3.1组;过表达SIRT3组移植瘤中Ki67的表达水平较pc DNA3.1组降低;过表达SIRT3上调Bax的m RNA和蛋白质水平并促进PARP的剪切。该文结果提示,SIRT3可能通过Bax凋亡信号通路抑制人肝细胞癌异位移植瘤的生长。
The aim of this study was to investigate the effect and mechanism of silent information regulator 3 (SIRT3) on the growth of hepatocellular carcinoma in nude mice model of human hepatocellular carcinoma xenotransplanted. To establish a SK-Hep-1 cell line stably overexpressing SIRT3 and pcDNA3.1. The cell suspensions stably overexpressing SIRT3 and pcDNA3.1 were injected subcutaneously into nude mice to monitor the growth of the transplanted tumors in both groups. 25 The tumor was excised and weighed. The expression of SIRT3 and Ki67 in the xenografts was detected by immunohistochemical staining. The downstream target molecules of SIRT3 that affect the growth of xenografts were screened by qRT-PCR. The expression of downstream target Bax and the expression level of cleaved-PARP (poly ADP-ribose polymerase) in xenografts. The results showed that the volume and weight of transplanted tumor in SIRT3 overexpression group were less than those in pcDNA3.1 group. The expression of Ki67 in the overexpressed SIRT3 group was lower than that in pcDNA3.1 group. Overexpression of SIRT3 upregulated the expression of m RNA and protein Level and promote the cleavage of PARP. The results suggest that SIRT3 may inhibit the growth of human hepatocellular carcinoma xenografts via Bax signaling pathway.