Research Papers:
Suppression of immune regulatory cells with combined therapy of celecoxib and sunitinib in renal cell carcinoma
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Abstract
Qi Zhao1, Jianming Guo1, Guomin Wang1, Yiwei Chu2, Xiaoyi Hu1
1Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
2Department of Immunology, Shanghai Medical College of Fudan University, Shanghai, 200032, China
Correspondence to:
Xiaoyi Hu, email: [email protected]
Jianming Guo, email: [email protected]
Keywords: tyrosine kinase inhibitor, renal cell carcinoma, cyclooxygenase-2 inhibitor, myeloid-derived suppressor cell, regulatory T cell
Received: August 15, 2016 Accepted: November 14, 2016 Published: December 02, 2016
ABSTRACT
Objective: To observe the the potential benefit of sunitinib in combination with cyclooxygenase-2(COX-2) inhibitor in renal cell carcinoma therapy.
Methods: 769-p cell lines were treated with sunitinib, celecoxib, or in combination at different concentrations respectively. We investigated the expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in 769-p and cell proliferation in vitro. BALB/c mice implanted with Renca cells were divided into 4 groups and administered orally by gavage with sunitinib, COX-2 inhibitor (celecoxib) monotherapy or combination, and PBS respectively. Tumor growth and animal survival were observed. The myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in peripheral blood and spleen were determined by flow cytometry. The MDSCs protein was extracted for STAT3 analysis by western blot.
Results: 769-p cell lines were suppressed in a dose and time-dependent manner. The expression of GM-CSF was substantially inhibited by celecoxib and sunitinib. Combination of sunitinib and celecoxib in vivo could effectively reduce the MDSCs than those in control group. Meanwhile, the CD4+ lymphocytes were strongly increased and the expression of signal transducer and activator of transcription 3 (STAT3) in MDSCs were significantly reduced.
Conclusion: Combination therapy with sunitinib and celecoxib intensified the curative effects to renal cell carcinoma by suppressing immune regulatory cells.
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PII: 13774