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

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 effec...

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Autores principales: Luo, Hongtao, Yang, Zhen, Zhang, Qiuning, Li, Tingdong, Liu, Ruifeng, Feng, Shuangwu, Liu, Zhiqiang, Sun, Shilong, Chen, Junru, Wang, Xiaohu, Xie, Xiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088534/
https://www.ncbi.nlm.nih.gov/pubmed/37057285
http://dx.doi.org/10.7150/jca.81222
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author Luo, Hongtao
Yang, Zhen
Zhang, Qiuning
Li, Tingdong
Liu, Ruifeng
Feng, Shuangwu
Liu, Zhiqiang
Sun, Shilong
Chen, Junru
Wang, Xiaohu
Xie, Xiaoling
author_facet Luo, Hongtao
Yang, Zhen
Zhang, Qiuning
Li, Tingdong
Liu, Ruifeng
Feng, Shuangwu
Liu, Zhiqiang
Sun, Shilong
Chen, Junru
Wang, Xiaohu
Xie, Xiaoling
author_sort Luo, Hongtao
collection PubMed
description 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.
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spelling pubmed-100885342023-04-12 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 J Cancer Research Paper 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. Ivyspring International Publisher 2023-02-22 /pmc/articles/PMC10088534/ /pubmed/37057285 http://dx.doi.org/10.7150/jca.81222 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Research Paper
Luo, Hongtao
Yang, Zhen
Zhang, Qiuning
Li, Tingdong
Liu, Ruifeng
Feng, Shuangwu
Liu, Zhiqiang
Sun, Shilong
Chen, Junru
Wang, Xiaohu
Xie, Xiaoling
LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway
title LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway
title_full LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway
title_fullStr LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway
title_full_unstemmed LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway
title_short LIF Inhibits Proliferation of Esophageal Squamous Carcinoma Cells by Radiation Mediated Through JAK-STAT Signaling Pathway
title_sort lif inhibits proliferation of esophageal squamous carcinoma cells by radiation mediated through jak-stat signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088534/
https://www.ncbi.nlm.nih.gov/pubmed/37057285
http://dx.doi.org/10.7150/jca.81222
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