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

2020 ◽  
Vol 8 ◽  
Author(s):  
Hongtao Luo ◽  
Zhen Yang ◽  
Qiuning Zhang ◽  
Lihua Shao ◽  
Shihong Wei ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Signaling Pathway ◽  
Ion Beam ◽  
Ion Beams ◽  
Dependent Manner ◽  
Carbon Ion ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Carbon Ion Beam ◽  
Dose Dependent

Radiation therapy is an important component of the comprehensive treatment of esophageal cancer. However, conventional radiation resistance is one of the main reasons for treatment failure. The superiority of heavy ion radiation in physics and biology has been increasingly highlighted in radiation therapy research. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway plays an important role in the occurrence, development and metastasis of esophageal squamous cell carcinoma (ESCC) and is related to the development of resistance to ionizing radiation in ESCC. Therefore, the aim of the present study was to investigate the relationship between carbon ion inhibition of the proliferation and metastasis of esophageal carcinoma cells and the JAK2/STAT3 signaling pathway. The results demonstrated that carbon ion beams significantly reduced cell viability and stimulated apoptosis in human ESCC cells in a dose-dependent manner. In addition, carbon ion beams induced G2/M phase cell cycle arrest in ESCC cells and inhibited tumor metastasis in a dose-dependent manner. Additionally, poorly differentiated KYSE150 cells were more sensitive to the same carbon ion beam dose than moderately differentiated ECA109 cells. Carbon ion beam exposure regulated the relative expression of metastasis-related molecules at the transcriptional and translational levels in ESCC cells. Carbon ion beams also regulated CDH1 and MMP2 downstream of the STAT3 pathway and inhibited ESCC cell metastasis, which activated the STAT3 signaling pathway. This study confirmed the inhibition of cell proliferation and the metastatic effect of carbon ion beam therapy in ESCC cells.

scholarly journals Brusatol, a Nrf2 Inhibitor Targets STAT3 Signaling Cascade in Head and Neck Squamous Cell Carcinoma

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 550 ◽  
Author(s):  
Jong Hyun Lee ◽  
Shobith Rangappa ◽  
Chakrabhavi Dhananjaya Mohan ◽  
Basappa ◽  
Gautam Sethi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factor ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Parp Cleavage ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

STAT3 is a latent transcription factor that plays a vital role in the transmission of extracellular signal from receptors to the nucleus. It has been regarded as a master transcription factor due to its role in the regulation of a broad spectrum of genes, which can contribute to oncogenesis. Persistent activation of STAT3 and deregulation of its signaling has been observed in various human cancers including head and neck squamous cell carcinoma (HNSCC). In the present work, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells. The data from the cell-based experiments suggested that BT-induced cytotoxicity and abrogated the activation of STAT3 and that of upstream kinases such as JAK1, JAK2, and Src. It reduced the levels of nuclear STAT3 and its DNA binding ability. BT treatment increased annexin-V-positive cells, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells. Taken together, brusatol can function as a promising inhibitor targeting STAT3 signaling pathway in HNSCC.

NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma

2020 ◽  
Vol 526 (1) ◽  
pp. 29-34
Author(s):  
Shutao Zheng ◽  
Qing Liu ◽  
Tao Liu ◽  
Lifei Yang ◽  
Qiqi Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Particle Beam Therapy for Cancer of the Skull Base, Nasal Cavity, and Paranasal Sinus

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Nobuyoshi Fukumitsu
Keyword(s):  
Nasal Cavity ◽  
Skull Base ◽  
Paranasal Sinus ◽  
Ion Beam ◽  
Particle Beam ◽  
Ion Beams ◽  
Carbon Ion ◽  
Carbon Ion Beam ◽  
Future Direction ◽  
Particle Beam Therapy

Particle beam therapy has been rapidly developed in these several decades. Proton and carbon ion beams are most frequently used in particle beam therapy. Proton and carbon ion beam radiotherapy have physical and biological advantage to the conventional photon radiotherapy. Cancers of the skull base, nasal cavity, and paranasal sinus are rare; however these diseases can receive the benefits of particle beam radiotherapy. This paper describes the clinical review of the cancer of the skull base, nasal cavity, and paranasal sinus treated with proton and carbon ion beams, adding some information of feature and future direction of proton and carbon ion beam radiotherapy.

scholarly journals Carbon-ion beam treatment induces systemic antitumor immunity against murine squamous cell carcinoma

Cancer ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 3740-3748 ◽  
Author(s):  
Akinao Matsunaga ◽  
Yasuji Ueda ◽  
Shigeru Yamada ◽  
Yui Harada ◽  
Hideaki Shimada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Antitumor Immunity ◽  
Ion Beam ◽  
Carbon Ion ◽  
Ion Beam Treatment ◽  
Carbon Ion Beam

scholarly journals Pentagalloylglucose Inhibits the Replication of Rabies Virus via Mediation of the miR-455/SOCS3/STAT3/IL-6 Pathway

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Zhongzhong Tu ◽  
Mengxian Xu ◽  
Jian Zhang ◽  
Ye Feng ◽  
Zhuo Hao ◽  
...  
Keyword(s):  
Viral Replication ◽  
Signaling Pathway ◽  
Rabies Virus ◽  
Antiviral Effect ◽  
Cytokine Signaling ◽  
Dependent Manner ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

ABSTRACT Our previous study showed that pentagalloylglucose (PGG), a naturally occurring hydrolyzable phenolic tannin, possesses significant anti-rabies virus (RABV) activity. In BHK-21 cells, RABV induced the overactivation of signal transducer and activator of transcription 3 (STAT3) by suppressing the expression of suppressor of cytokine signaling 3 (SOCS3). Inhibition of STAT3 by niclosamide, small interfering RNA, or exogenous expression of SOCS3 all significantly suppressed the replication of RABV. Additionally, RABV-induced upregulation of microRNA 455-5p (miR-455-5p) downregulated SOCS3 by directly binding to the 3′ untranslated region (UTR) of SOCS3. Importantly, PGG effectively reversed the expression of miR-455-5p and its following SOCS3/STAT3 signaling pathway. Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 in vitro and in vivo in a SOCS3/STAT3-dependent manner. Altogether, these data identify a new miR-455-5p/SOCS3/STAT3 signaling pathway that contributes to viral replication and IL-6 production in RABV-infected cells, with PGG exerting its antiviral effect by inhibiting the production of miR-455-5p and the activation of STAT3. IMPORTANCE Rabies virus causes lethal encephalitis in mammals and poses a serious public health threat in many parts of the world. Numerous strategies have been explored to combat rabies; however, their efficacy has always been unsatisfactory. We previously reported a new drug, PGG, which possesses a potent inhibitory activity on RABV replication. Herein, we describe the underlying mechanisms by which PGG exerts its anti-RABV activity. Our results show that RABV induces overactivation of STAT3 in BHK-21 cells, which facilitates viral replication. Importantly, PGG effectively inhibits the activity of STAT3 by disrupting the expression of miR-455-5p and increases the level of SOCS3 by directly targeting the 3′ UTR of SOCS3. Furthermore, the downregulated STAT3 inhibits the production of IL-6, thereby contributing to a reduction in the inflammatory response in vivo. Our study indicates that PGG effectively inhibits the replication of RABV by the miR-455-5p/SOCS3/STAT3/IL-6-dependent pathway.

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