| 引用本文: | 黄岚珍, 杨飞城, 阳 晶, 蒋晓山.莪术醇诱导人肝癌HepG2细胞衰老及其机制研究[J].广西植物,2018,38(7):894-902.[点击复制] |
| HUANG Lanzhen, YANG Feicheng, YANG Jing, JIANG Xiaoshan.Human hepatocarcinoma HepG2 cell senescence induced by curcumol and underlying mechanisms[J].Guihaia,2018,38(7):894-902.[点击复制] |
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| 莪术醇诱导人肝癌HepG2细胞衰老及其机制研究 |
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黄岚珍1,2, 杨飞城3, 阳 晶1,2, 蒋晓山1,4*
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1. 桂林医学院 信号转导实验室, 广西 桂林 541004;2. 桂林医学院 科学实验中心, 广西 桂林 541004;3. 桂林医学院
附属医院病理科, 广西 桂林 541004;4. 桂林医学院 研究生学院, 广西 桂林 541004
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| 摘要: |
| 为进一步探讨莪术醇的诱导细胞衰老的机制,该研究采用荧光定量PCR技术对莪术醇处理后细胞中 81 个细胞衰老相关基因差异表达谱进行分析,结果发现TP53及其下游基因p16Ink4a、p21Waf1/Cip1和p27Kip1等的表达水平显著升高,伴随ABL1、ALDH1A3、CHEK2、HRAS、PTEN等多个衰老信号通路启动与效应关联基因的转录显著增强,而Cyclin A2、IGFBP3、SIRT1以及TERT等细胞周期进程与衰老信号通路的负性调控基因的表达水平则显著降低。Western印迹检测结果显示,p53及其下游周期素依赖性蛋白激酶抑制物(CKI)分子p21WAF1和p16INK4水平升高,Cyclin A2水平降低,与PCR结果一致,并伴野生型p53-诱导的蛋白磷酸酶1(Wip1)水平显著增高,提示莪术醇可能通过激活p53信号通路诱导HepG2细胞衰老。该研究进一步发现莪术醇能够诱导HepG2细胞发生衰老表型改变,伴G0/G1期周期阻滞 |
| 关键词: 莪术醇, 肿瘤细胞早衰, HepG2细胞, 肝癌, 细胞周期阻滞 |
| DOI：10.11931/guihaia.gxzw201802029 |
| 分类号:Q946 |
| 文章编号:1000-3142(2018)07-0894-09 |
| 基金项目:国家自然科学基金(31660327); 广西医学科学实验中心开放基金(KFJJ2011-13)[Supported by the National Natural Science Foundation of China(31660327); Medical Science Research Center Open Fund(KFJJ2011-13)]。 |
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| Human hepatocarcinoma HepG2 cell senescence induced by curcumol and underlying mechanisms |
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HUANG Lanzhen1,2, YANG Feicheng3, YANG Jing1,2, JIANG Xiaoshan1,4*
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1. Cell Signaling Laboratory, Guilin Medical University, Guilin 541004, Guangxi, China;2. Center for Science Research, Guilin Medical
University, Guilin 541004, Guangxi, China;3. Department of Pathology, Affiliated Hospital, Guilin Medical University, Guilin
541004, Guangxi, China;4. Graduate College, Guilin Medical University, Guilin 541004, Guangxi, China
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| Abstract: |
| In order to further study the antitumor mechanism of curcumol and its potential clinical application, a SYBR Green real-time polymerase chain reaction(RT-PCR)method was used to analyze the differential expression profiles of 81 human senescence-related genes in human hepatocarcinoma HepG2 cells treated with curcumol. The results showed that the expression of TP53 and its downstream genes p16Ink4a, p21Waf1 / Cip1 and p27Kip1 were significantly up-regulated, accompanied by transactivation of other senescence signaling pathway related genes or senescence response genes such as ABL1, ALDH1A3, CHEK2, HRAS, PTEN, etc., while the expression of Cyclin A2, IGFBP3, SIRT1 and TERT, the genes which negatively regulated cell cycle progression and senescence signaling, were significantly down-regulated. Western blotting verified that protein levels of p53 and its downstream CKIs, p21WAF1 and p16INK4 increased while Cyclin A2 decreased, consistent with the findings in PCR results. The level of wild-type p53-induced protein phosphatase 1(Wip1)was also found significantly increased, suggesting that the induction of senescence in HepG2 cells by curcumol might be through activation of p53 signaling pathway. The present study further demonstrates that curcumol is capable of inducing cellular senescent phenotype in HepG2, accompanying with cell cycle G0 / G1 phase arrest. |
| Key words: curcumol, premature senescence of tumor cells, HepG2 cells, liver cancer, cell cycle arrest |
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