Efficacy of Arsenic Trioxide in the Treatment of Malignant Pleural Effusion Caused by Pleural Metastasis of Lung Cancer

Xie, Sheling; Yang, Mian; Chen, Kun; Huang, Hai; Zhao, Xia; Zang, Yuan‐Sheng; Li, Bing

doi:10.1007/s12013-014-0352-3

Cited by 21 publications

(14 citation statements)

References 23 publications

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“…We further constructed a mouse model of lung cancer accompanied by pleural metastasis. It was found that intrapleural injection of As 2 O 3 significantly inhibited the pleural vascular permeability and the microvascular density (MVD) in pleural tumor nodules, which led to the decrease of pleural metastasis and the formation of MPE [22]. In addition, we demonstrated that As 2 O 3 inhibited the growth of lung cancer xenografts, and the inhibitory effect in SCLC was particularly obvious.…”

Section: Introductionmentioning

confidence: 85%

Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling

et al. 2019

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Background The inhibitory effect of arsenic trioxide (As 2 O 3 ) on lung cancer has been reported in some preclinical studies. However, its effect on small cell lung cancer (SCLC) has been poorly explored. Calcineurin and its substrate, nuclear factor of activated T cells (NFAT), mediate the downstream signaling of VEGF, and is critical in the process endothelium activation and tumor metastasis. In this study, we aimed to evaluate whether As 2 O 3 had inhibitory effects on endothelial cells activation and the metastasis of SCLC, and to explore the possible mechanisms. Material/Methods In vitro , human umbilical vein endothelial cells (HUVECs) were used. Cell Counting Kit-8 assay and cell migration assay were performed to determine the effect of As 2 O 3 on HUVECs proliferation and migration. The level of calcineurin, NFAT, downstream factors for Down syndrome candidate region 1 (DSCR1), and the endogenous inhibitor of calcineurin, were evaluated by quantitative PCR and western blotting. In vivo , SCLC metastasis models were established by injecting NCI-H446 cells into tail veins of nude mice. Tumor-bearing mice were treated with As 2 O 3 or calcineurin inhibitor for 10 days, after which tumor metastasis in target organs was evaluated. Results As 2 O 3 significantly inhibited the proliferation and migration of endothelial cells. Also, As 2 O 3 inhibited the expression levels of calcineurin, NFAT, and the downstream target genes CXCR7 and RND1, while it upregulated the level of DSCR1. Both As 2 O 3 and calcineurin inhibitor exhibited notable inhibitory effect on the metastasis of SCLC, without obvious side effects. Conclusions These findings suggested that As 2 O 3 had remarkable inhibitory effects on the endothelial cell activation and SCLC metastasis, and the mechanism might be related to the blocking of calcineurin-NFAT signaling by upregulating DSCR1.

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Section: Introductionmentioning

confidence: 85%

Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling

et al. 2019

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“…demonstrated that As 2 O 3 could be highly effective in the treatment of acute promyelocytic leukemia (APL), and increasing studies have shown that it can induce complete remission, even in patients with relapsed APL, at low doses and with minimal general toxicity [ 8 ]. In other studies, As 2 O 3 has been shown to exert cytotoxic effects on a variety of tumors, such as lung cancer [ 9 ], nasopharyngeal carcinoma [ 10 ], osteosarcoma [ 11 ], neurogliocytoma [ 12 ], hepatoma [ 13 ], cervical cancer [ 14 ], cholangiocarcinoma [ 15 ], breast cancer [ 16 ], gastric cancer [ 17 ] and ovarian cancer [ 18 ]. These effects have been documented in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Xiong

Liu

et al. 2018

Biol Res

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BackgroundArsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB.MethodsThe aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis.ResultsImmunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3 significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined.ConclusionThe present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.

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“…Currently, inhibition of angiogenesis has become an important target in the treatment of solid tumors, including lung cancer (31,32 Our group has previously demonstrated that As 2 O 3 exhibits anti-lung cancer activity by inhibiting angiogenesis (33). It was also demonstrated that As 2 O 3 could reduce malignant pleural effusion caused by the pleural metastasis of lung cancer by downregulating nuclear factor-κB, tumor necrosis factor-α and VEGF-A (34). In the present study, the antitumor activity and anti-angiogenic effect of As 2 O 3 were demonstrated on both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in vivo.…”

Section: Introductionmentioning

confidence: 99%

Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation

et al. 2017

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Abstract. Arsenic trioxide (As 2 O 3 ) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As 2 O 3 on lung cancer and explored its possible mechanism. It was observed that As 2 O 3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As 2 O 3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As 2 O 3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-β, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As 2 O 3 . These findings suggested that anti-angiogenesis may be an underlying mechanism of As 2 O 3 anticancer activity in lung cancer.

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Efficacy of Arsenic Trioxide in the Treatment of Malignant Pleural Effusion Caused by Pleural Metastasis of Lung Cancer

Cited by 21 publications

References 23 publications

Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling

Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation

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