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Effect of bone-marrow-derived mesenchymal stem cells on high-potential hepatocellular carcinoma in mouse models: an intervention study
Li, Tianran1; Song, Bin1; Du, Xiangke2; Wei, Zhengmao2; Huo, Tianlong2
关键词Bone-marrow-derived Mesenchymal Stem Cells Osteopontin Bone Sialoprotein Integrins High Metastatic Potential Cell Animal Model
刊名EUROPEAN JOURNAL OF MEDICAL RESEARCH
2013-09-30
DOI10.1186/2047-783X-18-34
18
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]HEPATOCYTE-LIKE CELLS
英文摘要

Background: There are two completely contradictory views regarding the impact of human bone-marrow-derived mesenchymal stem cells (hMSCs) on hepatocellular carcinomas (HCCs). The aim of this study was to investigate the effect of hMSC engraftment on HCC tissues in nude mouse models, and assess the effect on metastatic potential of HCC.

Methods: hMSCs were engrafted into the nude mouse models of high metastatic HCC via the tail vein. The mice in the experimental group were engrafted with hMSCs (5 x 105 cells per mouse) via the tail vein 15 days after inoculation of tumor cells, twice a week, while the animals in the control group were injected with hMSC culture medium (0.2 mL per mouse) via the tail vein. The subcutaneous tumor size was measured using an electronic digital caliper once every 4 days after hMSC engraftment. After 2, 3, 4, 5 and 6 weeks of tumor cell inoculation, the mice were killed and the tumors were collected in their entirety. The tumor weights and body weights of mice were measured, and the tumor inhibition rate was calculated. Quantitative real-time polymerase chain reaction (RT-PCR) was used to determine the expression of metastasis-related genes including osteopontin (OPN), bone sialoprotein (BSP) and integrin a5 subunit (a-V) in the mouse models of high-metastatic HCC, and the expression of apoptosis-related genes including B cell lymphoma/leukemia-2 (Bcl2), Bcl-2 associated X protein (Bax) and caspase 3 in tumor samples.

Results: The tumor weight inhibition rate was 26.62% at 2 weeks, 52.00% at 3 weeks, 38.20% at 4 weeks, 31.98% at 5 weeks, and 30.23% at 6 weeks. Tumor tissue weight comparison results were significantly lower in the hMSC engraftment groups than in the control group at the second and third weeks. The expression of metastasis-related factors OPN, BSP and a-V gene was downregulated with time. The expression of antiapoptotic gene Bcl2 exhibited an obvious declining tendency, while the expression of apoptotic genes Bax and caspase 3 showed an obvious rising tendency. The expression of a-V and BSP significantly correlated positively with the expression of Bcl2, and negatively correlated with the expression of Bax and caspase 3. The tumor inhibition rate was not significantly correlated with the expression of antiapoptotic and apoptotic factors, and a-V and BSP factors, though it exhibited a significantly negative correlation with the expression of OPN.

Conclusions: The highest tumor inhibition rate was observed 3 weeks after hMSCs engraftment, and the tumor inhibition rate gradually reduced with the progression of time. The metastatic potential of tumor cells was downregulated after hMSC engraftment and hMSCs induce further tumor cells apoptosis. The decrease in the proliferation ability of tumor cells may induce a decline in metastatic potential in tumor cells.

语种英语
WOS记录号WOS:000325129600001
项目编号81271607
资助机构Chinese National Science Foundation
引用统计
被引频次:7[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/400002259/55636
专题北京大学第二临床医学院_放射科
作者单位1.PLA, Hosp 95, Dept Radiol, Putian 351100, Fujian Province, Peoples R China
2.Peking Univ Peoples Hosp, Dept Radiol, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Li, Tianran,Song, Bin,Du, Xiangke,et al. Effect of bone-marrow-derived mesenchymal stem cells on high-potential hepatocellular carcinoma in mouse models: an intervention study[J]. EUROPEAN JOURNAL OF MEDICAL RESEARCH,2013,18.
APA Li, Tianran,Song, Bin,Du, Xiangke,Wei, Zhengmao,&Huo, Tianlong.(2013).Effect of bone-marrow-derived mesenchymal stem cells on high-potential hepatocellular carcinoma in mouse models: an intervention study.EUROPEAN JOURNAL OF MEDICAL RESEARCH,18.
MLA Li, Tianran,et al."Effect of bone-marrow-derived mesenchymal stem cells on high-potential hepatocellular carcinoma in mouse models: an intervention study".EUROPEAN JOURNAL OF MEDICAL RESEARCH 18(2013).
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