Clinical & Translational Oncology
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2022
·Vol. 25
·期 3
·662-672
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IF 3.34
Chen Jing,Huang Shuting,Li Huawen,Li Yun,Zeng Haishan,Hu Jiemei,Lin Yanchun,Cai Huihua,Deng Pengfei,Song Ting,Guan Tian,Zeng Haoyu,Liu Mubiao
Purpose Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine
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2021
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IF 5.307
Xi Li,Qi Wang,Sihui Yu,Minyi Zhang,Xijian Liu,Guoying Deng,Yuan Liu,Sufang Wu
Background: Radiosensitizers that can effectively consume glutathione provide broad prospects for enhancing the efficacy and reducing the side effects of radiotherapy. Aim: To explore the potential role of CuS@mSiO2@MnO2 nanocomposites in synergetic chemoradiotherapy. Methods: Nanocomposites were characterized by transmission electron microscopy, UV-Vis spectrometry and dynamic light scattering and were loaded with doxorubicin (DOX). The uptake and biodistribution of nanocomposites were observed by CCK8 assay, MRI and confocal laser scanning microscopy. The radiosensitization effect of nanocomposites and nanocomposites/DOX was assessed both in vitro and in vivo. Results:In vitro application of nanocomposites, with an average diameter of 30 nm and ζ-potential of 13.2 ± 0.4 mV, in combination with radiotherapy, depleted glutathione and induced ferroptosis and apoptosis. Nanocomposites/DOX exhibited tumor cell damage in vivo. Conclusion: We propose that this glutathione-depleting nanosystem could be a radiosensitizer as well as a drug transporter.
研究领域:
纳米技术
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肿瘤学
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放射生物学
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药学
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DOI
PubMed
高影响因子
INFLAMMATION
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2020
·Vol. 43
·期 5
·1751-1758
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IF 3.212
Zhaohui Chen,Shuihua Wu
Accumulating evidence supports that Sirtuin 6 (SIRT6) may play a vital role in the pathogenesis of spinal cord injury. The current study was designed to investigate the specific effects of SIRT6 on spinal cord injury (SCI). HE and Nissl staining were performed for pathological analysis in SCI rats. SIRT6 expression was detected by RT-qPCR. CCK8 assay was applied for the detection of cell viability of LPS-injured PC12 cells. TNF-a, IL-1β, IL-6, MCP-1 levels and ROS, MPO, SOD levels were assessed to evaluate inflammation and oxidative stress in spinal cord injury. Cell apoptosis were evaluated by morphological examination using AO/EB fluorescent staining methods and key proteins related to apoptosis were explored via western blot. HE staining revealed increased cavity involving the dorsal white matter and central gray matter, and Nissl staining discovered the loss of motor neurons in the ventral horn in SCI rats. SIRT6 had lower expression in SCI rats. Lipopolysaccharide (LPS) exposure induced cell apoptosis and reduced the expression of SIRT6. Mechanistically, we revealed that up-regulation of SIRT6 alleviated inflammation and oxidative stress and inhibited cell apoptosis in spinal cord injury. Together, our findings indicated that SIRT6 attenuated spinal cord injury by suppressing inflammation, oxidative stress, and cell apoptosis. This study demonstrates that SIRT6 may represent a protective effect against spinal cord injury.
研究领域:
神经科学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
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2019
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IF 2.197
Hao Lu,Hui Yao,Rong Zou,Xiwen Chen,Hanlin Xu
Renal inflammation can result in renal injury. Uric acid (UA) is the final product of purine metabolism in humans and because of the lack of urate oxidase, UA may accumulate in tissues, including kidney, causing inflammation. Galangin was isolated from a traditional Chinese medicine plant and possesses several beneficial effects, working as an anti-oxidant, anti-mutagenic, anti-tumor, anti-inflammatory, anti-microbial, and anti-viral agent. Therefore, this study aimed at investigating the molecular mechanism of galangin in the attenuation of UA induced renal inflammation in normal rat kidney epithelial cells NRK-52E. Our findings suggested that galangin treatment efficiently protected NRK-52E cells against UA induced renal inflammation by decreasing tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, prostaglandin E2 (PGE2), and nitric oxide (NO) release, and it inhibited nitric oxide synthase (iNOS), prostaglandin endoperoxide synthase 2 (PTGS2), TNF-α, IL-1β, and IL-18 mRNA expression. In addition, galangin was not exerting any cytotoxicity at the concentrations that were effective against inflammation as assessed by CCK8 assay. Moreover, western blotting showed that galangin treatment effectively inhibited nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) signaling pathway activation. Taken together, these findings suggested that galangin plays a pivotal role in renal inflammation by suppressing inflammatory responses, which might be closely associated with the inhibition of NLRP3 inflammasome, NF-κB and PI3K/AKT signaling pathway activation.
研究领域:
药理学
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肾病学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
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