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学科主题基础医学
YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma
Kong, Jian1; Kong, Fandong1; Gao, Jun1; Zhang, Qiangbo6; Dong, Shuying1; Gu, Fang7; Ke, Shan1; Pan, Bing2,3,4; Shen, Qiang2,3,4; Sun, Huichuan5; Zheng, Lemin2,3,4; Sun, Wenbing1
关键词Yc-1 Sorafenib Hepatocellular Carcinoma Stat3
刊名MOLECULAR CANCER
2014-01-13
DOI10.1186/1476-4598-13-7
13
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Oncology
研究领域[WOS]Biochemistry & Molecular Biology ; Oncology
关键词[WOS]INDUCIBLE FACTOR-1 ALPHA ; CANCER CELL-LINE ; IN-VIVO ; APOPTOSIS ; PATHWAY ; RESISTANCE ; RECEPTOR ; GROWTH ; METASTASIS ; ANTICANCER
英文摘要

Background: Traditional systemic chemotherapy does not provide survival benefits in patients with hepatocellular carcinoma (HCC). Molecular targeted therapy shows promise for HCC treatment, however, the duration of effectiveness for targeted therapies is finite and combination therapies offer the potential for improved effectiveness.

Methods: Sorafenib, a multikinase inhibitor, and YC-1, a soluble guanylyl cyclase (sGC) activator, were tested in HCC by proliferation assay, cell cycle analysis and western blot in vitro and orthotopic and ectopic HCC models in vivo.

Results: In vitro, combination of sorafenib and YC-1 synergistically inhibited proliferation and colony formation of HepG2, BEL-7402 and HCCLM3 cells. The combination also induced S cell cycle arrest and apoptosis, as observed by activated PARP and caspase 8. Sorafenib and YC-1 respectively suppressed the expression of phosphorylated STAT3 (p-STAT3) (Y705) in a dose-and time-dependent manner. Combination of sorafenib and YC-1 significantly inhibited the expression of p-STAT3 (Y705) (S727), p-ERK1/2, cyclin D1 and survivin and SHP-1 activity compared with sorafenib or YC-1 used alone in all tested HCC cell lines. In vivo, sorafenib-YC-1 combination significantly suppressed the growth of HepG2 tumor xenografts with decreased cell proliferation and increased apoptosis observed by PCNA and PARP. Similar results were also confirmed in a HCCLM3 orthotopic model. There was a reduction in CD31-positive blood vessels and reduced VEGF expression, which suggested a combinational effect of sorafenib and YC-1 on angiogenesis. The reduced expression of p-STAT3, cyclin D1 and survivin was also observed with the combination of sorafenib and YC-1.

Conclusions: Our data show that sorafenib-YC-1 combination is a novel potent therapeutic agent that can target the STAT3 signaling pathway to inhibit HCC tumor growth.

语种英语
WOS记录号WOS:000331564200001
项目编号320675007131 ; 32067501207 ; 2010CB912504 ; 2011CB503900 ; 81170101 ; 81370235 ; 30821001 ; 7122106
资助机构Dr. Jieping Wu Medical Foundation ; Program for Medical Key Discipline of Shijingshan District, Beijing ; "973" National ST Major Project ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing, China
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56545
专题北京大学基础医学院_心血管所
北京大学基础医学院
作者单位1.Capital Med Univ, Beijing Chaoyang Hosp, Dept Hepatobiliary Surg, Beijing 100043, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Inst Cardiovasc Sci,Educ Minist,Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Inst Syst Biomed,Educ Minist,Sch Basic Med Sci, Beijing 100191, Peoples R China
4.Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 100191, Peoples R China
5.Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200032, Peoples R China
6.Shandong Univ, Qilu Hosp, Dept Gen Surg, Jinan 250012, Peoples R China
7.Chinese Peoples Liberat Army Gen Hosp, Dept Obstet & Gynecol, Beijing 100853, Peoples R China
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GB/T 7714
Kong, Jian,Kong, Fandong,Gao, Jun,et al. YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma[J]. MOLECULAR CANCER,2014,13.
APA Kong, Jian.,Kong, Fandong.,Gao, Jun.,Zhang, Qiangbo.,Dong, Shuying.,...&Sun, Wenbing.(2014).YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma.MOLECULAR CANCER,13.
MLA Kong, Jian,et al."YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma".MOLECULAR CANCER 13(2014).
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