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学科主题临床医学
B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells
Zhang, Wei; Wang, Jing; Wang, Yanfang; Dong, Fei; Zhu, Mingxia; Wan, Wenli; Li, Haishen; Wu, Feifei; Yan, Xinxing; Ke, Xiaoyan1,2
关键词B7-h3 Acute Monocytic Leukemia Cancer Gene Therapy Chemosensitivity
刊名ONCOTARGETS AND THERAPY
2015
DOI10.2147/OTT.S85272
8页:1721-1733
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Oncology
研究领域[WOS]Biotechnology & Applied Microbiology ; Oncology
关键词[WOS]ACUTE MYELOID-LEUKEMIA ; COSTIMULATORY MOLECULE ; MONOCYTIC LEUKEMIA ; PANCREATIC-CANCER ; INDUCED APOPTOSIS ; LUNG-CANCER ; EXPRESSION ; OVEREXPRESSION ; SENSITIVITY ; METASTASIS
英文摘要

Background: The role of B7-H3 in acute monocytic leukemia U937 cells has not been thoroughly investigated.

Materials and methods: B7-H3 knockdown in the U937 cell line was performed using small hairpin (sh)RNA lentivirus transduction. The effects on cell proliferation, cycle, migration, and invasion were investigated by Cell Counting Kit-8 assay, methyl cellulose colony-forming assay, propidium iodide staining, and Transwell assays in vitro. Changes in cell growth inhibition and apoptosis, when combined with chemotherapy drugs, were determined using the Cell Counting Kit-8 and Annexin V-FITC/PI assays. U937 xenograft models were used to assess the effects of B7-H3 on tumorigenicity and the therapeutic effect of B7-H3 knockdown in combination with chemotherapy drugs in vivo.

Results: Downregulation of B7-H3 significantly decreased U937 cell growth and colony-forming ability. The mean inhibition rate of tumor growth with B7-H3 knockdown was 59.4%, and the expression of both Ki-67 and PCNA in xenografts was significantly reduced. After B7-H3 silencing, the U937 cell cycle was arrested at the G0/G1 phase. The cell migration rate of B7-H3 knockdown cells was reduced more than fivefold, and invasion capacity decreased by 86.7%. B7-H3 RNAi profoundly increased the antitumor effect of chemotherapy in vitro and in vivo. On day 19, inhibition rates of tumor growth in B7-H3 shRNA combined with idarubicin, cytarabine, and idarubicin plus cytarabine were 70.5%, 80.0%, and 90.0%, respectively (P=0.006, P=0.004, and P=0.016, respectively).

Conclusion: B7-H3 may promote U937 cell progression, and shRNA targeting B7-H3 significantly enhances sensitivity to chemotherapeutic drugs. These results may provide new insight into the function of B7-H3 and a promising therapeutic approach targeting B7-H3 in acute monocytic leukemia.

语种英语
WOS记录号WOS:000357878800006
项目编号81172245
资助机构National Natural Science Foundation of China
引用统计
被引频次:16[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/400002259/54207
专题北京大学第三临床医学院_血液内科
作者单位1.Peking Univ, Hosp 3, Dept Hematol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Lymphoma Res Ctr, Beijing 100191, Peoples R China
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Zhang, Wei,Wang, Jing,Wang, Yanfang,et al. B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells[J]. ONCOTARGETS AND THERAPY,2015,8:1721-1733.
APA Zhang, Wei.,Wang, Jing.,Wang, Yanfang.,Dong, Fei.,Zhu, Mingxia.,...&Ke, Xiaoyan.(2015).B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells.ONCOTARGETS AND THERAPY,8,1721-1733.
MLA Zhang, Wei,et al."B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells".ONCOTARGETS AND THERAPY 8(2015):1721-1733.
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