Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis
文献类型：期刊论文
| 作者 | Zhao, Jian1,2; Dong, Li1,2,3,4; Liu, Bin1,2; Wu, Guobin1,2,5; Xu, Dongmei3; Chen, Jingjing1,2; Li, Kai1,2; Tong, Xin1,2; Dai, Jianxin1,2; Yao, Side3 |
| 刊名 | Gastroenterology
 |
| 出版日期 | 2008-09-01 |
| 卷号 | 135期号:3页码:956-968 |
| ISSN号 | 0016-5085 |
| DOI | 10.1053/j.gastro.2008.05.025 |
| 通讯作者 | Guo, yajun(yjguo@smmu.edu.cn) |
| 英文摘要 | Background & aims: expression of osteopontin correlates with tumor progression and metastasis. the mechanisms by which osteopontin promotes tumor cell survival remain unclear. here we used short-hairpin rna-mediated gene silencing to investigate the antitumor effects by osteopontin depletion in hepatocellular carcinoma (hcc). methods: we applied polyethylenimine nanoparticles to deliver a short-hairpin rna for depletion of osteopontin expression in hcc cells. tumorigenicity and metastatic potentials of hcc cells were studied in vitro and in nude mice. nuclear factor-kappa b (nf-kappa b) activation was analyzed by gel shift assay and luciferase analysis. the expressions of integrins were examined by real-time reverse-transcription polymerase chain reaction. apoptosis was examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and mitochondrial membrane potential analysis. results: down-regulation of osteopontin inhibited hcc cell growth, anchorage-independent growth, adhesion with fibronectin and invasion through extracellular matrix in vitro, and suppressed tumorigenicity and lung metastasis in nude mice. osteopontin silencing resulted in suppression of alpha v, beta 1, and beta 3 integrin expressions, blockade of nf-kappa b activation, inhibition of bcl-2/bcl-xl and xiap expressions, increase of bax expression, and induction of a mitochondria-mediated apoptosis. furthermore, down-regulation of osteopontin inhibited drug-induced nf-kappa b activation and sensitized hcc cells to chemotherapeutic agents in vitro, which led to complete regression of hcc xenografts in nude mice. conclusions: osteopontin may facilitate tumorigenesis and metastasis through prevention of tumor cells from apoptosis. rna interference-mediated depletion of osteopontin may be a promising strategy for the treatment of hcc by sensitizing the chemotherapeutic drugs. |
| WOS关键词 | NF-KAPPA-B ; IN-VIVO ; POLYMERIC NANOPARTICLES ; TUMOR PROGRESSION ; GENE DELIVERY ; CANCER-CELLS ; ACTIVATION ; EXPRESSION ; SURVIVAL ; THERAPY |
| WOS研究方向 | Gastroenterology & Hepatology |
| WOS类目 | Gastroenterology & Hepatology |
| 语种 | 英语 |
| WOS记录号 | WOS:000259099300037 |
| 出版者 | W B SAUNDERS CO-ELSEVIER INC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2389885 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Guo, Yajun |
| 作者单位 | 1.Second Mil Med Univ, Int Canc Inst, Shanghai 200433, Peoples R China 2.Second Mil Med Univ, Eastern Hosp Hepatobiliary Surg, Shanghai 200433, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai, Peoples R China 4.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 5.Guangxi Med Univ, Guangxi Canc Hosp, Guangxi, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Jian,Dong, Li,Liu, Bin,et al. Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis[J]. Gastroenterology,2008,135(3):956-968. |
| APA | Zhao, Jian.,Dong, Li.,Liu, Bin.,Wu, Guobin.,Xu, Dongmei.,...&Guo, Yajun.(2008).Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis.Gastroenterology,135(3),956-968. |
| MLA | Zhao, Jian,et al."Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis".Gastroenterology 135.3(2008):956-968. |
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来源：中国科学院大学
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