LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway

Luo, Hongtao; Yang, Zhen; Zhang, Qiuning; Li, Tingdong; Liu, Ruifeng; Feng, Shuangwu; Liu, Zhiqiang; Sun, Shilong; Chen, Junru; Wang, Xiaohu; Xie, Xiaoling

doi:10.7150/jca.81222

International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

open access Global reach, higher impact

Full Text | PDF

J Cancer 2023; 14(4):532-543. doi:10.7150/jca.81222 This issue Cite

Research Paper

LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway

Hongtao Luo^1,3#, Zhen Yang^1,2#, Qiuning Zhang^1,3, Tingdong Li⁴, Ruifeng Liu^1,3, Shuangwu Feng¹, Zhiqiang Liu^1,3, Shilong Sun^1,3, Junru Chen¹, Xiaohu Wang^1,3,4✉, Xiaoling Xie⁵

1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
2. School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
3. Lanzhou Heavy Ion Hospital, Lanzhou, China.
4. Gansu Provincial Cancer Hospital, Lanzhou, China.
5. The Central Laboratory of the First Hospital of Lanzhou University, Lanzhou, China.
^#These authors contributed equally to this work.

Citation:

Luo H, Yang Z, Zhang Q, Li T, Liu R, Feng S, Liu Z, Sun S, Chen J, Wang X, Xie X. LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway. J Cancer 2023; 14(4):532-543. doi:10.7150/jca.81222. https://www.jcancer.org/v14p0532.htm

Other styles

Abstract

Background: Esophagus cancer is a malignant tumor with a high incidence rate, and radiation is an important modality for esophageal cancer therapy. However, therapeutic failure in the treatment of ESCC is often attributed to an inherent radio-resistance of the tumor cells. This study discusses effect and mechanism of carbon ion exerts tumor-inhibiting proliferation via down-regulation of LIF in esophageal squamous cell carcinoma.

Methods: Colony formation, CCK8 and EdU assays were used to detect cell survival and proliferation after 0 and 2Gy carbon ion irradiation of ECA109 cells. Proteomics changes were probed in response to carbon ion irradiation using quantitative proteomics approach incorporating TMT isotope tags. Then, candidate genes were identified via bioinformatics analysis methods and microarray results were verified by real-time qPCR. Paired ESCC tumor tissues and adjacent non-tumor samples from 17 patients were collected and used for detecting expression by immunohistochemistry. Furthermore, small interfering RNA (siRNA) was transfected into ECA109 and KYSE150 cells and cell proliferation was analyzed by EdU assay. Flow cytometry and Western blot were performed to measure the and apoptosis and JAK-STAT3 protein expression level of ECA109 and KYSE150 cells combined drugs after siLIF transfection.

Results: When compared with the control (0Gy), Inhibition of ECA109 cell proliferation and clonogenic survival by 2 Gy carbon ions, radiation group screened 360 differentially expressed proteins, 156 of which were up-regulated and 144 were down-regulated. Downregulation of LIF expression by siRNA enhances apoptotic in the ECA109 and KYSE150 cells, significantly inhibited esophageal squamous cell carcinoma cells proliferation. In ESCC cells, the JAK/STAT3 signaling pathway is inhibited in a LIF-dependent manner, resulting in the expression of STAT3 downstream target genes. Carbon ions combined with siLIF inhibited cell proliferation more significantly. The inhibitory cell proliferation effect was more pronounced by the combined intervention of carbon ion irradiation with siLIF. LIF expression was 18.51±9.84 and 5.82±4.50 in 17 paired ESCC tissues and adjacent non-cancerous tissues, respectively. LIF protein expression was lower in ESCC than in the adjacent normal tissue.

Conclusion: The findings of this study reveal that Carbon ion knockdown was shown to downregulate LIF in ESCC cells. LIF is involved in ESCC proliferation and inhibited the ESCC cell proliferation by activating the STAT3 signaling pathways.

Keywords: Carbon ion, Esophageal squamous cell carcinoma, Proteomics, LIF

Citation styles

APA

Luo, H., Yang, Z., Zhang, Q., Li, T., Liu, R., Feng, S., Liu, Z., Sun, S., Chen, J., Wang, X., Xie, X. (2023). LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway. Journal of Cancer, 14(4), 532-543. https://doi.org/10.7150/jca.81222.

ACS

Luo, H.; Yang, Z.; Zhang, Q.; Li, T.; Liu, R.; Feng, S.; Liu, Z.; Sun, S.; Chen, J.; Wang, X.; Xie, X. LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway. J. Cancer 2023, 14 (4), 532-543. DOI: 10.7150/jca.81222.

NLM

CSE

Luo H, Yang Z, Zhang Q, Li T, Liu R, Feng S, Liu Z, Sun S, Chen J, Wang X, Xie X. 2023. LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway. J Cancer. 14(4):532-543.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.