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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2018.00631

Oxymatrine and Cisplatin Synergistically Enhance Anti-tumor Immunity of CD8+ T Cells in Non-small Cell Lung Cancer

Jin Ye1,  Man-Man Zou1,  Pei Li1,  Xi-Jun Lin1,  Qi-Wei Jiang2, Yang Yang2,  Jia-Rong Huang2,  Meng-Ling Yuan2, Zi-Hao Xing2,  Meng-Ning Wei2, Yao Li2,  Zhi Shi2* and Hui Liu1*
  • 1Sun Yat-sen University, China
  • 2Jinan University, China

Oxymatrine (OMT) has shown broad antitumor activities for the treatment of several types of cancers. However, little is known about its effect on anti-tumor immunity. Combination therapy is a potentially promising strategy of cancer to enhance anticancer activity, overcome drug resistance, and lower treatment failure rate. In the present study, we demonstrated that the combination of OMT with cisplatin (DDP) synergistically inhibited non-small cell lung cancer (NSCLC) cells growth when co-cultured with peripheral blood mononuclear cells in vitro. Furthermore, the combination of OMT with DDP significantly inhibited the growth of Lewis lung cancer (LLC) mouse xenograft tumors. Flow cytometry analysis revealed that OMT and DDP synergistically increase the CD8+/ regulatory T cells ratio and enhanced more CD8+ T cells secreted cytokines of IFN-γ, TNF-α and IL-2 in vivo. Mechanistically, upregulation of miR-155 and downregulation of suppressor of cytokine signaling-1 (SOCS1) were confirmed as a target signaling pathway to positively regulate the anti-tumor response of CD8+ T cells. Overall, OMT in combination with DDP showed outstanding synergistic anti-tumor immunity, suggesting that this beneficial combination may offer a potential immunotherapy for NSCLC patients.

Keywords: Oxymatrine, Cisplatin, CD8+ T cells, anti-tumor immunity, NSCLC

Received: 12 Nov 2018; Accepted: 04 Dec 2018.

Edited by:

Yan-yan YAN, Shanxi Datong University, China

Reviewed by:

Hua Zhu, Wexner Medical Center, The Ohio State University, United States
Xiao Qian Chen, Huazhong University of Science and Technology, China  

Copyright: © 2018 Ye, Zou, Li, Lin, Jiang, Yang, Huang, Yuan, Xing, Wei, Li, Shi and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Zhi Shi, Jinan University, Guangzhou, China, tshizhi@jnu.edu.cn
Prof. Hui Liu, Sun Yat-sen University, Guangzhou, 510275, Guangdong Province, China, liuhui27@mail.sysu.edu.cn