Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma

查看全文 作　　者：Fan [1,2]Feng;Yin-Ying [1]Lu;Fan [3]Zhang;Xu-Dong [1]Gao;Chuan-Fu [4]Zhang;Alex [5]Meredith;Zhong-Xian [1]Xu;Yu-Tao [6]Yang;Xiu-Juan [1]Chang;Hong [1]Wang;Jian-Hui [1]Qu;Zhen [1]Zeng;Jun-Lan [3]Yang;Chun-Ping [1]Wang;Yun-Feng [3]Zhu;Jia-Jun [4,5]Cui;Yong-Ping [1]Yang

机构地区：[1]Clinical Research Center of Hepatocarcinoma,302 Military Hospital;[2]Institute of Toxicology and Pharmacology,Chinese Academy of Military Medical Sciences;[3]Tumor Center,PLA General Hospital;[4]Institute of Disease Control and Prevention,Chinese Academy of Military Medical Sciences;[5]Department of Cancer and Cell Biology,University of Cincinnati College of Medicine,Cincinnati,OH 45267,United States;[6]Beijing Institute for Neuroscience,Capital Medical University

出　　处：《World Journal of Gastroenterology》索引2013年第19卷第7期,共11页

基　　金：Supported by The Key Scientific and Technological Research Foundation of the National Special Purpose Program,No.2008ZX10002-018 摘　　要：AIM:To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1(LINE-1),ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma(HCC) cells.METHODS:MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells.Cell proliferation inhibition and the IC 50 were calculated by the Origin 8.0 software.Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes,including p53,p27,p15,Bcl-2,mdr,and p-gp.To corroborate the proliferation and anchor-independent growth results,the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF1p on the apoptosis regulation.RESULTS:LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs(cisplatin and epirubicin) in HepG2 cells.The IC 50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L.Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin.The IC 50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L.Interestingly,down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel.The IC 50 decreased from 35.90 nmol/L to 7.36 nmol/L.However,overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells.Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression.As a protein arrested in the nucleus,LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors.Indeed,LINE-1 ORF-1p promoted HepG2 cell proliferation,anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15,p21,p53,and Bcl-2 genes.CONCLUSION:LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs.By establishing novel roles and defining the mechanisms of LINE-1 ORF1p in HCC chemotherapeutic drug resistance and cell proliferation regulation,this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance. 关键词：LONG interspersed NUCLEAR element-1 ORF-1 PROTEIN Hepatocellular carcinoma Chemotherapeutic drugs Multi-drug RESISTANCE

相关文献

参考文献（21）
引证文献（9）
耦合文献（9）

参考文献(21)

引证文献(9)

耦合文献(9)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma

参考文献(21)

引证文献(9)

耦合文献(9)

用户提示