J Cancer 2021; 12(15):4638-4647. doi:10.7150/jca.56185

Research Paper

IL-11 mediates the Radioresistance of Cervical Cancer Cells via the PI3K/Akt Signaling Pathway

Ruige Sun1,2*, Chunli Chen2*, Xinzhou Deng2, Fengqin Wang2, Shimao Song2, Qiang Cai3, Jincheng Wang4, Te Zhang5, Mingliang Shi6, Qing Ke2✉, Zhiguo Luo2✉

1. Postgraduate Training Basement of Jinzhou Medical University, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province 442000, China.
2. Department of Clinical Oncology, Taihe Hospital, Shiyan City, Hubei Province 442000, China.
3. Graduate School of Guangxi Medical University, Nanning, Guangxi, 530021, China.
4. Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan City, Hubei Province 442000, China.
5. Biomedical Research Institute, Hubei University of Medicine, Shiyan City, Hubei Province 442000, China.
6. Department of Gastroenterology, Zhushan People's Hospital, Shiyan City, Hubei Province 442000, China.
*These authors contributed equally to this work.

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Citation:
Sun R, Chen C, Deng X, Wang F, Song S, Cai Q, Wang J, Zhang T, Shi M, Ke Q, Luo Z. IL-11 mediates the Radioresistance of Cervical Cancer Cells via the PI3K/Akt Signaling Pathway. J Cancer 2021; 12(15):4638-4647. doi:10.7150/jca.56185. Available from https://www.jcancer.org/v12p4638.htm

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Abstract

Cervical cancer is one of the most common malignant tumors in the female reproductive system. Radioresistance remains a significant factor that limits the efficacy of radiotherapy for cervical cancer. Interleukin‐11 (IL-11) has been reported to be upregulated in various types of human cancer and correlate with clinical stage and poor survival. However, the exact effects and mechanisms of IL-11 in the radioresistance of cervical cancer have not yet been defined. In this research, TCGA databases revealed that IL-11 expression was upregulated in cervical cancer tissues and was associated with clinical stages and poor prognosis in cervical cancer patients. We discovered that IL-11 concentration was significantly upregulated in radioresistant cervical cancer cells. Knocking down IL-11 in Hela cells could reduce clonogenic survival rate, decrease cell viability, induce G2/M phase block, and facilitate cell apoptosis. In contrast, Exogeneous IL-11 in C33A cells could upregulate clonogenic survival rate, increase cell viability, curb G2/M phase block, and cell apoptosis. Mechanistic investigations showed that radioresistance conferred by IL-11 was attributed to the activation of the PI3K/Akt signaling pathway. Altogether, our results demonstrate that IL-11 might be involved in radioresistance, and IL-11 may be a potent radiosensitization target for cervical cancer therapy.

Keywords: cervical cancer, radioresistance, IL-11, radiotherapy