STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1α

Zhang, Chi; Yang, Xi; Qu, Zhilin; Guo, Qing; He, Jia; Qin, Qin; Zhu, Hongcheng; Liu, Jia; Li, Zhan; Lü, Jing; Liu, Zheming; Xu, Liping; Ma, Jianxin; Dai, Shengbin; Cheng, Hongyan; Sun, Xinchen

doi:10.1007/s13277-014-2207-3

Cited by 33 publications

(17 citation statements)

References 20 publications

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“…Yang et al found that celecoxib suppresses the phosphorylation of STAT3 protein expression and can enhance the radiosensitivity of medulloblastoma-derived cancer stem-like cells [31]. Zhang et al reported that the STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer cells via the downregulation of HIF-1α [32]. In this study, we found that the overexpression of miR-124 enhanced the radiosensitivity of NSCLC cells.…”

Section: Discussionsupporting

confidence: 53%

MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3

Wang

Meng

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: A growing body of evidence indicates that the abnormal expression of microRNAs (miRNAs) play an important role in sensitizing the cellular response to ionizing radiation (IR). The aim of this study was to investigate whether the expression of miR-124 correlated with radiosensitivity in the context of non-small-cell lung carcinoma (NSCLC). Methods: Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-124 expression in NSCLC tissues and cell lines. The role of miR-124 in NSCLC proliferation and radiosensitivity was analyzed using CCK-8 and flow cytometry apoptosis assays. Luciferase activity assays, RT-PCR, and Western blot assays were performed to confirm the target gene of miR-124. Results: In this study, we found that miR-124 was downregulated both in clinical NSCLC samples and in cell lines. miR-124 inhibited the proliferation of NSCLC cells and enhanced the apoptosis of NSCLC cells exposed to ionizing radiation. We identified signal transducer and activator of transcription 3 (STAT3) as a direct target of miR-124 by using target prediction algorithms and luciferase assays. Overexpression of STAT3 in A549 cell lines restored the enhanced radiosensitivity induced by miR-124. Conclusion: Taking these observations into consideration, we illustrated that miR-124 is a potential target for enhancing the radiosensitivity of NSCLC cells by targeting STAT3.

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Section: Discussionsupporting

confidence: 53%

MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3

Wang

Meng

Liu

et al. 2017

Cell Physiol Biochem

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“…STAT3 is constitutively activated in many human cancers with poor prognosis or chemo- or radio-resistance, which have been molecularly linked through cancer genome landscape studies to increased tyrosine kinase signaling in particular [41–43]. Aberrant STAT3 signaling is an important process in malignant progression.…”

Section: Discussionmentioning

confidence: 99%

MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling

et al. 2016

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Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q up-regulated tyrosine kinase signaling through PDGFR signaling, which was blockable by imatinib. In conclusion, we demonstrated that enhanced AF1q expression contributes to persistent and oncogenic pYSTAT3 levels in invasive carcinoma cells by activating Src kinase through activation of the PDGF-B/PDGFR cascade. Therefore, AF1q plays an essential role as a cofactor in PDGF-B-driven STAT3 signaling.

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“…A large body of clinical evidence suggests that tumor hypoxia negatively impacts radiotherapy, so there much research has been conducted into novel methods of improving tumor oxygenation, targeting hypoxic tumor cells, and modulating the response of hypoxic tumors to radiation [44, 45]. As more has been learned about the many ways hypoxia affects tumors, our understanding of the mechanisms connecting hypoxia to radio-sensitivity has become increasingly broad and complex [45, 46]. This has opened up new potential avenues for interrupting the negative effects of hypoxia on tumor radio-sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment

et al. 2015

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Hypoxia decreases cytotoxic responses to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. Cellular prion protein (PrPc) is regulated by HIF-1α in neurons. We hypothesized that PrPc is involved in hypoxia-mediated resistance to TRAIL-induced apoptosis. We found that hypoxia induced PrPc protein and inhibited TRAIL-induced apoptosis. Thus silencing of PrPc increased TRAIL-induced apoptosis under hypoxia. Overexpression of PrPc protein using an adenoviral vector inhibited TRAIL-induced apoptosis. In xenograft model in vivo, shPrPc transfected cells were more sensitive to TRAIL-induced apoptosis than in shMock transfected cells. Molecular chemo-therapy approaches based on the regulation of PrPc expression need to address anti-tumor function of TRAIL under hypoxia. Molecular chemo-therapy approaches based on the regulation of PrPc expression need to address anti-tumor function of TRAIL under hypoxia.

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STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1α

Cited by 33 publications

References 20 publications

MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3

MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3

MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment

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