Carbon Ion Therapy Inhibits Esophageal Squamous Cell Carcinoma Metastasis by Upregulating STAT3 Through the JAK2/STAT3 Signaling Pathway

Luo, Hui; Yang, Zhen; Zhang, Qiuning; Shao, Lihua; Wei, Shihong; Liu, Ruifeng; Li, Zheng; Geng, Yichao; Li, Chengcheng; Wang, Xiaohu

doi:10.3389/fpubh.2020.579705

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…We observed that the colony formation rate of A549 cells irradiated with carbon ion rays was significantly lower, and the colony formation rate and survival fraction of A549 cells were significantly lower after irradiation at each dose (1, 2, and 4 Gy) compared with 0 Gy, especially this change was most pronounced at 4 Gy. Carbon ions could inhibit the proliferation of A549 cells, and the activity of A549 cells was the lowest at 24 h after irradiation, as we previously observed in esophageal cancer ( 21 ). Secondly, we studied the effect of carbon ion irradiation on the metastasis of A549 cells, and analyzed the migration and invasion of A549 cells after carbon ion irradiation.…”

Section: Discussionsupporting

confidence: 78%

Effect of Carbon Ion Radiation Induces Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis

et al. 2021

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ObjectiveTo analyze the effect of carbon ion (12C6+) radiation may induce bystander effect on A549 cell metastasis and metabonomics.MethodsA549 cell was irradiated with carbon ion to establish the clone survival model and the transwell matrix assay was applied to measure the effect of carbon ion on cell viability, migration, and invasion, respectively. Normal human embryonic lung fibroblasts (WI-38) were irradiated with carbon ions of 0 and 2 Gy and then transferred to A549 cell co-culture medium for 24 h. The migration and invasion of A549 cells were detected by the Transwell chamber. The analysis of metabonomic information in transfer medium by liquid phase mass spectrometry (LC-MS), The differential molecules were obtained by principal pomponent analysis (PCA) and the target proteins of significant differences (p = 1.7 × 10−3) obtained by combining with the STICH database. KEGG pathway was used to analyze the enrichment of the target protein pathway.ResultsCompared with 0 Gy, the colony formation, migration, and invasion of A549 cells were significantly inhibited by carbon ion 2 and 4 Gy irradiation, while the inhibitory effect was not significant after 1 Gy irradiation. Compared with 0 Gy, the culture medium 24 h after carbon ion 2 Gy irradiation significantly inhibited the metastasis of tumor cells (p = 0.03). LC-MS analysis showed that 23 differential metabolites were obtained in the cell culture medium 24 h after carbon ion 0 and 2 Gy irradiation (9 up-regulated and 14 down-regulated). Among them, two were up-regulated and two down-regulated (p = 2.9 × 10−3). 41 target proteins were corresponding to these four differential molecules. Through the analysis of the KEGG signal pathway, it was found that these target molecules were mainly enriched in purine metabolism, tyrosine metabolism, cysteine and methionine metabolism, peroxisome, and carbon metabolism. Neuroactive ligand-receptor interaction, calcium signaling pathway, arachidonic acid metabolism, and Fc epsilon RI signaling pathway.ConclusionThe bystander effect induced by 2 Gy carbon ion radiation inhibits the metastasis of tumor cells, which indicates that carbon ions may change the metabolites of irradiated cells, so that it may indirectly affect the metabolism of tumor cell growth microenvironment, thus inhibiting the metastasis of malignant tumor cells.

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Section: Discussionsupporting

confidence: 78%

Effect of Carbon Ion Radiation Induces Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis

et al. 2021

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“…Another study found that miR-21 could promote STAT3 by binding to the STAT3 promoter. All those studies suggest that miR-21 is closely related to the activation of the JAK2/STAT3 signaling pathway (23). In our study, the levels of JAK2 and STAT3 mRNA in the DUSP1 OVG of CC cells were significantly reduced compared with those in the C33a COG.…”

Section: Discussionsupporting

confidence: 50%

DUSP1 regulates the JAK2/STAT3 signaling pathway through targeting miR-21 in cervical cancer cells

Hailin Chen,

Songsen Ren,

Hui Wan

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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“…Our previous carbon ion irradiation studies of ESCC cells in different differentiation states found that a high dose of carbon ions prolongs G2/M cell cycle arrest, promotes apoptosis, and inhibits cell proliferation significantly. Carbon ion inhibiting sustained STAT3 activation via blocking of the JAK2/STAT3 signaling pathway, which leads to inhibition of migration and invasion in ESCC cells 11 .…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, carbon ion rays induced significant necrosis in the central region of the tumor, but X-ray induced only mild necrosis [10]. We have previously found that carbon ion radiation promotes apoptosis and inhibits cell proliferation in esophageal squamous carcinoma cells through cell experiments [11]. However, high LET radiation causes more complex protein modification changes through posttranslational and oxidative processes, making the specific targets and mechanisms of radiation-mediated biological phenotypes remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Luo¹,

Yang²,

Zhang³

et al. 2023

J. Cancer

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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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Carbon Ion Therapy Inhibits Esophageal Squamous Cell Carcinoma Metastasis by Upregulating STAT3 Through the JAK2/STAT3 Signaling Pathway

Cited by 10 publications

References 41 publications

Effect of Carbon Ion Radiation Induces Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis

Effect of Carbon Ion Radiation Induces Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis

DUSP1 regulates the JAK2/STAT3 signaling pathway through targeting miR-21 in cervical cancer cells

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

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