目的检测氯化两面针碱(NC)对人肝癌细胞基因表达情况的影响。方法建立人肝癌HepG2裸鼠移植瘤模型,应用基因芯片技术分析NC治疗肝癌后基因表达谱的改变,应用实时荧光定量PCR(Real time PCR)方法验证基因芯片结果。结果 NC能明显抑制人肝...目的检测氯化两面针碱(NC)对人肝癌细胞基因表达情况的影响。方法建立人肝癌HepG2裸鼠移植瘤模型,应用基因芯片技术分析NC治疗肝癌后基因表达谱的改变,应用实时荧光定量PCR(Real time PCR)方法验证基因芯片结果。结果 NC能明显抑制人肝癌裸鼠移植瘤的生长。NC组与生理盐水组比较,差异表达基因共有369个,其中上调基因183个,下调基因186个。与细胞凋亡、细胞周期相关的基因IHPK2、PR48、MTSS1等上调,Bcl 2L2、AMID、RTEL1 CCNT2等下调,Real time PCR结果显示基因表达的改变与芯片研究结果具有一致性。结论差异表达基因涉及细胞增殖与凋亡调控、细胞周期、肿瘤免疫相关、分裂/增殖、DNA损伤/修复等多个方面的功能。NC作用于肝癌的基因调控是一个多基因、多环节、多途径参与的过程。展开更多
BRCA1 has been proposed to be tightly linked to the resistance of tumor cells to ionizing radiation. The pathway leading to this phenomenon is not yet clear. In this work, we investigated the role of BRCA1 in the apop...BRCA1 has been proposed to be tightly linked to the resistance of tumor cells to ionizing radiation. The pathway leading to this phenomenon is not yet clear. In this work, we investigated the role of BRCA1 in the apoptosis regulation in response to carbon ion irradiation. We utilized three different cancer cell lines with various states for BRCA1 and p53 to identify the rela- tionship between endogenous BRCA1 and the apoptosis-related genes, and determine whether p53 function would affect the role of BRCA1 in apoptosis regulation. By Western blot analysis, we found that Bax expressions were not significantly changed after irradiation in all of three cell lines. However, Bcl-2 expression showed an up-regulation by endogenous BRCA1 regardless of p53 status. Moreover, the changes in Bcl-2 protein were due to the increase in the transcriptional levels of Bcl-2 mRNA, based on real-time PCR assay. At the same time, BRCAl-deficient cells showed a greater apoptosis susceptibility to irradiation when compared with BRCAl-proficient cells. The results suggest that BRCA1 might exert p53-independent regulative activities for Bcl-2, which seems account for the low apoptosis susceptibility in BRCAl-proficient carcinomas.展开更多
文摘目的检测氯化两面针碱(NC)对人肝癌细胞基因表达情况的影响。方法建立人肝癌HepG2裸鼠移植瘤模型,应用基因芯片技术分析NC治疗肝癌后基因表达谱的改变,应用实时荧光定量PCR(Real time PCR)方法验证基因芯片结果。结果 NC能明显抑制人肝癌裸鼠移植瘤的生长。NC组与生理盐水组比较,差异表达基因共有369个,其中上调基因183个,下调基因186个。与细胞凋亡、细胞周期相关的基因IHPK2、PR48、MTSS1等上调,Bcl 2L2、AMID、RTEL1 CCNT2等下调,Real time PCR结果显示基因表达的改变与芯片研究结果具有一致性。结论差异表达基因涉及细胞增殖与凋亡调控、细胞周期、肿瘤免疫相关、分裂/增殖、DNA损伤/修复等多个方面的功能。NC作用于肝癌的基因调控是一个多基因、多环节、多途径参与的过程。
基金supported by the National Basic Research Program of China (Grant No. 2010CB834202)National Natural Science Foundation of China (Grant Nos. 10835011 and 10805064)+1 种基金Special Foundation of President of the Chinese Academy of Sciencesthe External Cooperation Program of Chinese Academy of Sciences,Japan Society for the Promotion of Science and NIRS for Cooperative Research Program
文摘BRCA1 has been proposed to be tightly linked to the resistance of tumor cells to ionizing radiation. The pathway leading to this phenomenon is not yet clear. In this work, we investigated the role of BRCA1 in the apoptosis regulation in response to carbon ion irradiation. We utilized three different cancer cell lines with various states for BRCA1 and p53 to identify the rela- tionship between endogenous BRCA1 and the apoptosis-related genes, and determine whether p53 function would affect the role of BRCA1 in apoptosis regulation. By Western blot analysis, we found that Bax expressions were not significantly changed after irradiation in all of three cell lines. However, Bcl-2 expression showed an up-regulation by endogenous BRCA1 regardless of p53 status. Moreover, the changes in Bcl-2 protein were due to the increase in the transcriptional levels of Bcl-2 mRNA, based on real-time PCR assay. At the same time, BRCAl-deficient cells showed a greater apoptosis susceptibility to irradiation when compared with BRCAl-proficient cells. The results suggest that BRCA1 might exert p53-independent regulative activities for Bcl-2, which seems account for the low apoptosis susceptibility in BRCAl-proficient carcinomas.
