Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer

You, Sylvaine; Li, Rui; Park, Dongkyoo; Xie, Mengying; Sica, Gabriel L.; Cao, Yang; Xiao, Zhi‐Qiang; Deng, Xingming

doi:10.1158/1535-7163.mct-13-0608

Cited by 159 publications

(131 citation statements)

References 39 publications

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“…Furthermore, Bcl-2 and Bax have been reported to be downstream factors of STAT3, and they serve important roles in the mitochondrial-mediated apoptosis pathway (18,20). Bcl-2 is an anti-apoptotic protein and Bax is a pro-apoptotic protein.…”

Section: Discussionmentioning

confidence: 99%

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Celastrol suppresses the proliferation of lung adenocarcinoma cells by regulating microRNA-24 and microRNA-181b

Yan

Zhang

et al. 2017

Oncol Lett

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Abstract. Cumulative evidence has indicated that celastrol may suppress cancer growth; however, the underlying mechanism requires further investigation. In the present study, A549 cells were treated with various concentrations of celastrol. Lung cancer cell proliferation was evaluated using an MTT assay and observed under a microscope. Cell apoptosis was detected by Annexin V fluorescein isothiocyanate/propidium iodide double-labeled flow cytometry. The results demonstrated that celastrol suppressed proliferation and induced apoptosis in a dose-independent manner. Celastrol may also decrease the phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and the B cell lymphoma-2 (Bcl-2)/Bcl-2 associated C protein (Bax) ratio. As microRNA (miR-24 and miR-181b) were predicated to target STAT3, STAT3 activation was inhibited in miR-24-or miR-181b-treated A549 cells compared with the control treatment. The ratio of Bcl-2/Bax was further reduced in miR-24 or miR-181b-treated A549 cells. The results were further confirmed by detecting in another lung adenocarcinoma cell line, LTEP-a-2. In summary, the results of the present study demonstrated that celastrol treatment suppressed the proliferation and induced apoptosis by regulating the expression levels of miR-24 and miR-181b.

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Section: Discussionmentioning

confidence: 99%

“…The optical density (OD) value was determined using an ELISA reader (ELx800; Bio-Tek Instruments, Inc., Winooski, VT, USA) at 570 nm. Cell growth inhibition rate = (OD control -OD sample)/OD control x100 (%) (17,18).…”

Section: Methodsmentioning

confidence: 99%

Celastrol suppresses the proliferation of lung adenocarcinoma cells by regulating microRNA-24 and microRNA-181b

Yan

Zhang

et al. 2017

Oncol Lett

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“…Niclosamide (C13H8Cl2N2O4) is a small-molecule drug of the teniacide anthelmintic family that is effective against human tapeworms (14,15). This agent was previously reported to have therapeutic activities in several cancers by inhibition of STAT3 (14,16,17).…”

Section: Introductionmentioning

confidence: 99%

“…This agent was previously reported to have therapeutic activities in several cancers by inhibition of STAT3 (14,16,17). However, there have been no reports evaluating whether inhibiting STAT3 signaling using this drug could modify the sensitivity to platinums in ovarian cancers.…”

Section: Introductionmentioning

confidence: 99%

JAK2/STAT3 pathway as a therapeutic target in ovarian cancers

et al. 2018

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Abstract. The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.

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“…The development of radioresistance in NSCLC cells limits the effectiveness of radiotherapy to treat patients with NSCLC (35). Therefore, the present study examined the effect of miR-148b expression on irradiation-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑148b inhibits proliferation and the epithelial‑mesenchymal transition and increases radiosensitivity in non‑small cell lung carcinomas by regulating ROCK1

Luo

Liang

2018

Exp Ther Med

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Abstract. Non-small cell lung cancer (NSCLC) accounts for ~80% of all types of lung cancer, which has the highest morbidity and mortality of all types of cancer worldwide. It is important to identify novel biomarkers and the molecular mechanism of NSCLC to improve current treatments of NSCLC. The present study aimed to investigate the effect of miR-148b expression on the proliferation, epithelial-mesenchymal transition (EMT) and radiosensitivity of NSCLC cells. It was demonstrated that miR-148b expression was significantly decreased in NSCLC tissues and cell lines. A549 cells were then transfected with a miR-148b mimic and a miR-148b inhibitor. Transfection with the miR-148b mimic decreased proliferation whereas transfection with the miR-148b inhibitor increased the proliferation of A549 cells. Additionally, the miR-148b mimic increased E-cadherin expression and decreased N-cadherin and vimentin expression. By contrast, transfection with the miR-148b inhibitor decreased E-cadherin expression and increased N-cadherin and vimentin expression. Irradiation-induced cell death was significantly promoted by the miR-148b mimic but inhibited by the miR-148b inhibitor. The miR-148b mimic significantly decreased the expression of Rho-associated protein kinase 1 (ROCK1) and it was demonstrated that overexpression of ROCK1 significantly inhibited the effects of miR-148b on cell proliferation, the EMT and irradiation-induced cell death. Therefore, the current study revealed that miR-148b inhibited NSCLC cell proliferation and the EMT, and increased the radiosensitivity of NSCLC cells by inhibiting ROCK1 expression. Therefore, miR-148b/ROCK1 signaling may be a novel therapeutic target to inhibit the growth of NSCLC cells and enhance the effects of radiotherapy to treat patients with NSCLC.

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Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer

Cited by 159 publications

References 39 publications

Celastrol suppresses the proliferation of lung adenocarcinoma cells by regulating microRNA-24 and microRNA-181b

Celastrol suppresses the proliferation of lung adenocarcinoma cells by regulating microRNA-24 and microRNA-181b

JAK2/STAT3 pathway as a therapeutic target in ovarian cancers

MicroRNA‑148b inhibits proliferation and the epithelial‑mesenchymal transition and increases radiosensitivity in non‑small cell lung carcinomas by regulating ROCK1

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