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Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma

  • Authors:
    • Xin Zhao
    • Guang-Bo Zhang
    • Wen-Juan Gan
    • Feng Xiong
    • Zhi Li
    • Hua Zhao
    • Dong-Ming Zhu
    • Bin Zhang
    • Xue-Guang Zhang
    • De-Chun Li

  • View Affiliations

  • Published online on: January 8, 2013     https://doi.org/10.3892/ol.2013.1118
  • Pages: 805-812
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Abstract

In numerous types of cancer, the expression of a novel member of the B7 ligand family, the B7‑H3 immunoregulatory protein, has been correlated with a poor prognosis. In the present study, we investigated the role of B7-H3 in chemoresistance in pancreatic carcinoma. Silencing of B7-H3, through lentivirus-mediated delivery of stable short hairpin RNA, was observed to increase the sensitivity of the human pancreatic carcinoma cell line Patu8988 to gemcitabine as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 caused the cancer cells to be more resistant to the drug. Subsequently, we investigated the underlying mechanisms of B7-H3-mediated gemcitabine resistance, and found that the levels of survivin decreased in cells in which B7-H3 had been knocked down. In vivo animal experiments demonstrated that tumors in which B7-H3 had been knocked down displayed a slower growth rate compared with the control xenografts. Notably, gemcitabine treatment led to a strong antitumor activity in mice with tumors in which B7-H3 had been knocked down; however, this effect was only marginal in the control group. Furthermore, survivin expression was weak in gemcitabine-treated tumors in which B7-H3 had been knocked down and apoptosis was increased, as revealed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining. In summary, the present study demonstrated that B7-H3 induces gemcitabine resistance in pancreatic carcinoma cells, at least partially by downregulating survivin expression. These results provide novel insights into the function of B7-H3 and encourage the design and investigation of approaches targeting this protein in treating pancreatic carcinoma.
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March 2013
Volume 5 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Journal Metrics
  • Impact Factor: 2.9
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 6.3
  • CiteScore Rank: Q2: #119/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.725
  • SCImago Journal Rank (SJR): 0.639
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Spandidos Publications style
Zhao X, Zhang G, Gan W, Xiong F, Li Z, Zhao H, Zhu D, Zhang B, Zhang X, Li D, Li D, et al: Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma. Oncol Lett 5: 805-812, 2013
APA
Zhao, X., Zhang, G., Gan, W., Xiong, F., Li, Z., Zhao, H. ... Li, D. (2013). Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma. Oncology Letters, 5, 805-812. https://doi.org/10.3892/ol.2013.1118
MLA
Zhao, X., Zhang, G., Gan, W., Xiong, F., Li, Z., Zhao, H., Zhu, D., Zhang, B., Zhang, X., Li, D."Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma". Oncology Letters 5.3 (2013): 805-812.
Chicago
Zhao, X., Zhang, G., Gan, W., Xiong, F., Li, Z., Zhao, H., Zhu, D., Zhang, B., Zhang, X., Li, D."Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma". Oncology Letters 5, no. 3 (2013): 805-812. https://doi.org/10.3892/ol.2013.1118