Oncotarget

Research Papers:

B7-H3 combats apoptosis induced by chemotherapy by delivering signals to pancreatic cancer cells

Dongbao Li, Jun Wang, Jian Zhou, Shenghua Zhan, Yang Huang, Fei Wang, Zixiang Zhang, Dongming Zhu, Hua Zhao, Dechun Li, Gang Chen, Xinguo Zhu and Xin Zhao _

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Oncotarget. 2017; 8:74856-74868. https://doi.org/10.18632/oncotarget.20421

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Abstract

Dongbao Li1,2,3,4,5,*, Jun Wang6,*, Jian Zhou1,2,*, Shenghua Zhan7, Yang Huang1,2,4,5, Fei Wang1, Zixiang Zhang1,2, Dongming Zhu1,2, Hua Zhao1, Dechun Li1,2, Gang Chen8, Xinguo Zhu1 and Xin Zhao1,2,4,5

1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

2Pancreatic Disease Research Center, The First Affiliated Hospital of Soochow University, Suzhou, China

3Department of HBP, Suzhou Dushuhu Public Hospital, Soochow University Multi-Disciplinary Polyclinic, Suzhou, China

4Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China

5Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China

6Department of Emergency, The First Affiliated Hospital of Soochow University, Suzhou, China

7Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China

8Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China

*These authors have contributed equally to this work

Correspondence to:

Xin Zhao, email: zhaox@suda.edu.cn

Xinguo Zhu, email: zxg45@hotmail.com

Gang Chen, email: chen.gang@wmu.edu.cn

Keywords: chemotherapy resistance, gemcitabine, Panc-1, pancreatic cancer, patu8988

Received: April 13, 2017    Accepted: June 18, 2017    Published: August 24, 2017

ABSTRACT

Objective: This study aimed to investigate the role of B7-H3 in chemotherapy resistance of pancreatic cancer cells and discover the potential signal transduction pathway and molecular targets involved.

Methods: Immunohistochemical staining and real-time polymerase chain reaction (PCR) were used to determine the expression of B7-H3 in clinical specimens. Clinical data were applied to survival analysis. Phosphoprotein was purified from cultured Patu8988 cells using the Phosphoprotein Purification Kit. Cell apoptosis was detected using propidium iodide–Annexin V staining to investigate the relation between the expression of B7-H3 and Patu8988 cells treated with gemcitabine. Western blot was used to determine the effect of B7-H3 on the expression of proteins including extracellular signal–regulated kinase (ERK)1/2, epidermal growth factor receptor (EGFR), and Inhibitor of NF-κB(IκB) in Patu8988 cells; B7-H3 was activated by 4H7, which as an agonist monoclonal antibody to B7-H3.

Results: The expression of B7-H3 was found to be higher in tumor tissues than in normal tissues of pancreatic carcinoma. Survival analysis revealed that patients in the low-B7-H3 expression group were likely to have a longer overall survival compared with those in the high-expression group (P < 0.05). B7-H3 activated by 4H7 could reduce gemcitabine-induced apoptosis in Patu8988 cells. Activation of B7-H3 by 4H7 induced variations in p-ERK1/2, EGFR, and IκB protein levels. When B7-H3 was upregulated, the expression levels of EGFR and p-ERK1/2 proteins significantly increased (P < 0.05), but the expression level of IκB significantly decreased (P < 0.05), especially in the gemcitabine-treated group.

Conclusion: This study demonstrated that B7-H3 could deliver signals to pancreatic cancer cells to combat apoptosis induced by gemcitabine.


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