J Cancer 2015; 6(10):962-969. doi:10.7150/jca.12266

Research Paper

Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells

Sen Wang1, #, ✉, Weifang An1,#, Yunhong Yao1, #, Renhuai Chen1, Xiaoxuan Zheng1,2, Wanyong Yang2, Yi Zhao1, Xinrong Hu1, Enping Jiang1, Yanhong Bie3, Zhangquan Chen1, Ping Ouyang1, He Zhang1, Hui Xiong1

1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
2. Clinical Laboratory, Guanghua hospital, Dongguan 523808, China;
3. Pathology, People's Hospital of Xiaolan, Zhongshan 528415, China.
# The three authors contribute equally to this work and are co-first authors.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Wang S, An W, Yao Y, Chen R, Zheng X, Yang W, Zhao Y, Hu X, Jiang E, Bie Y, Chen Z, Ouyang P, Zhang H, Xiong H. Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells. J Cancer 2015; 6(10):962-969. doi:10.7150/jca.12266. Available from http://www.jcancer.org/v06p0962.htm

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Objectives: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC).

Materials and methods: HPV+ Hela cells and HPV- C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1β. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively.

Results: Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV+ Hela cells than that in HPV- C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1β, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1β.

Conclusions: IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

Keywords: Interleukin 37, Cervical cancer, Proliferation, Invasion.