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学科主题: 基础医学
题名:
Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis
作者: Pan, Yan1,2; Zhong, Li-jun3; Zhou, Hong1,2; Wang, Xin1,2; Chen, Kui1,2; Yang, Hao-peng1,2; Xiaokaiti, Yilixiati1,2; Maimaiti, Aikebaier1,2; Jiang, Ling1,2; Li, Xue-jun1,2
关键词: heparin ; cell growth ; proteome ; vimentin ; 14-3-3 zeta/delta ; alpha(v)-integrin
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2012-06-01
DOI: 10.1038/aps.2012.42
卷: 33, 期:6, 页:798-808
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: MOLECULAR-WEIGHT HEPARIN ; LUNG-CANCER ; ADHESION
英文摘要:

Aim: To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin.

Methods: Human prostate cancer PC-3M cells were incubated with heparin 0.5 to 125 mu g/mL for 24 h. The proliferation of PC-3M cells was assessed by MTS assay. BrdU incoporation and Ki67 expression were detected using a high content screening (HCS) assay. The cell cycle and apoptosis of PC-3M cells were tested by flow cytometry. B16-F10-luc-G5 cardinoma cells were injected into the lateral tail vein of 6-week old male Balb/c nude mice and heparin 30 mg/kg was administered iv 30 min before and 24 h after injection. The metasis of B16-F10-luc-G5 cells was detected by bioluminescence assay. Activated partial thromboplastin time (APTT) and hemorheological parameters were measured on d 14 after injection of B16-F10-luc-G5 carcinoma cells in Balb/c mice. The global protein changes in PC-3M cells and frozen lung tissues from mice burdened with B16-F10-luc-G5 cells were determined by 2-dimensional gel electrophoresis and image analysis. The protein expression of vimentin and 14-3-3 zeta/delta was measured by Western blot. The mRNA transcription of vimentin, transforming growth factor (TGF)-beta, E-cadherin, and alpha(v)-integrin was measured by RT-PCR.

Results: Heparin 25 and 125 mu g/mL significantly inhibited the proliferation, arrested the cells in G(1) phase, and suppressed BrdU incorporation and Ki67 expression in PC-3M cells compared with the model group. But it had no significant effect on apoptosis of PC-3M cells. Heparin 30 mg/kg markedly inhibits the metastasis of B16-F10-luc-G5 cells on day 8. Additionally, heparin administration maintained relatively normal red blood hematocrit but had no influence on APTT in nude mice burdened with B16-F10-luc-G5 cells. Thirty of down-regulated protein spots were identified after heparin treatment, many of which are related to tumor development, extracellular signaling, energy metabolism, and cellular proliferation. Vimentin and 14-3-3 zeta/delta were identified in common in PC-3M cells and the lungs of mice bearing B16-F10-luc-G5 carcinoma cells. Heparin 25 and 125 mu g/mL decreased the protein expression of vimentin and 14-3-3 zeta/delta and the mRNA expression of alpha(v)-integrin. Heparin 125 mu g/mL decreased vimentin and E-cadherin mRNA transcription while increased TGF-beta mRNA transcription in the PC-3M cells, but the differences were not significant. Transfection of vimentin-targeted siRNA for 48 h significantly decreased the BrdU incoporation and Ki67 expression in PC-3M cells.

Conclusion: Heparin inhibited PC-3M cell proliferation in vitro and B16-F10-luc-G5 cells metastasis in nude mice by inhibition of vimentin, 14-3-3 zeta/delta, and alpha(v)-integrin expression.

语种: 英语
所属项目编号: 81020108031 ; 30572202 ; 30973558 ; 30772571 ; 30901815 ; 30901803 ; 2009ZX09103-144 ; B07001
项目资助者: National Natural Science Foundation of China ; Ministry of Science and Technology in China ; Ministry of Education of China ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
WOS记录号: WOS:000305034500011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63398
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China
2.Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China
3.Peking Univ, Ctr Med Anal, Beijing 100191, Peoples R China

Recommended Citation:
Pan, Yan,Zhong, Li-jun,Zhou, Hong,et al. Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis[J]. ACTA PHARMACOLOGICA SINICA,2012,33(6):798-808.
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