title: B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells.
abstract: BACKGROUND
  The role of B7-H3 in acute monocytic leukemia U937 cells has not been thoroughly investigated.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Haishen
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ke
keywords: B7-H3; acute monocytic leukemia; cancer gene therapy; chemosensitivity