|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|
|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|
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.
|资助机构||National Natural Science Foundation of China|
|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
|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.|