JAK2 inhibitor combined with DC-activated AFP-specific T-cells enhances antitumor function in a Fas/FasL signal-independent pathway
Authors Liu Y, Wang Y, Ding G, Yang T, Yao L, Hua J, He Z, Qian M
Received 9 October 2015
Accepted for publication 7 March 2016
Published 20 July 2016 Volume 2016:9 Pages 4425—4433
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Norbert Ajeawung
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Yang Liu,1 Yue-ru Wang,2 Guang-hui Ding,1 Ting-song Yang,1 Le Yao,1 Jie Hua,1 Zhi-gang He,1 Ming-ping Qian1
1Department of Hepatobiliary Surgery, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Infection, Shanghai First People’s Hospital Affiliated to Jiaotong University, Shanghai, People’s Republic of China
Objective: Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated α-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8+ T-cells combined with or without JAK2 inhibitor.
Methods: Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway.
Results: We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8+ T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells.
Conclusion: These results indicate a Fas/FasL-independent pathway for cellular apoptosis in cancer therapies with the treatment of AFP-specific CD8+ T-cells combined with JAK2 inhibitor.
Keywords: AFP-specific CD8+ T-cells, JAK2 inhibitor, Fas/FasL signal, antitumor, apoptosis
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