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

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

doi:10.3892/ol.2013.1118

March 2013 Volume 5 Issue 3

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March 2013 Volume 5 Issue 3

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Article

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 / Copyright

Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Clinic Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Intervention Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Pages: 805-812
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Published online on: January 8, 2013

https://doi.org/10.3892/ol.2013.1118
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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