Stimuli-responsive release and efficient siRNA delivery in non-small cell lung cancer by a poly(l-histidine)-based multifunctional nanoplatform

2020 ◽  
Vol 8 (8) ◽  
pp. 1616-1628 ◽  
Author(s):  
Menghao Shi ◽  
Jiulong Zhang ◽  
Ziyuan Huang ◽  
Yuying Chen ◽  
Shuang Pan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Silencing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Sirna Delivery ◽  
Small Cell ◽  
Proton Sponge ◽  
Stimuli Responsive ◽  
Small Cell Lung

A stimuli-responsive nanoplatform achieves successful intracellular siRNA delivery due to a proton sponge effect based on poly(l-histidine) and effective gene silencing in vivo.

scholarly journals Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment

2015 ◽  
Vol 112 (25) ◽  
pp. 7779-7784 ◽  
Author(s):  
Xi Zhu ◽  
Yingjie Xu ◽  
Luisa M. Solis ◽  
Wei Tao ◽  
Liangzhe Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Small Cell ◽  
Solid Polymer ◽  
Small Cell Lung ◽  
Formidable Challenge

RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery. The new generation lipid–polymer hybrid NPs are small and uniform, and can efficiently encapsulate siRNA and control its sustained release. They exhibit long blood circulation (t1/2 ∼8 h), high tumor accumulation, effective gene silencing, and negligible in vivo side effects. With this RNAi NP, we delineate and validate the therapeutic role of Prohibitin1 (PHB1), a target protein that has not been systemically evaluated in vivo due to the lack of specific and effective inhibitors, in treating non-small cell lung cancer (NSCLC) as evidenced by the drastic inhibition of tumor growth upon PHB1 silencing. Human tissue microarray analysis also reveals that high PHB1 tumor expression is associated with poorer overall survival in patients with NSCLC, further suggesting PHB1 as a therapeutic target. We expect this long-circulating RNAi NP platform to be of high interest for validating potential cancer targets in vivo and for the development of new cancer therapies.

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

scholarly journals Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1510-1523
Author(s):  
Ying Wang ◽  
Mimi Guo ◽  
Dingmei Lin ◽  
Dajun Liang ◽  
Ling Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preparation And Evaluation

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

scholarly journals Arsenic sulfide reverses cisplatin resistance in non‐small cell lung cancer in vitro and in vivo through targeting PD‐L1

2021 ◽  
Vol 12 (19) ◽  
pp. 2551-2563
Author(s):  
Wei Tian ◽  
Yinping Sun ◽  
Yuping Cheng ◽  
Xiao Ma ◽  
Weina Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Arsenic Sulfide ◽  
Small Cell Lung

scholarly journals Combination of baicalein and docetaxel additively inhibits the growth of non-small cell lung cancer in vivo

2018 ◽  
Vol 01 (03) ◽  
pp. 213-218 ◽  
Author(s):  
Linwei Lu ◽  
Zhengxiao Zhao ◽  
Lumei Liu ◽  
Weiyi Gong ◽  
Jingcheng Dong
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Bearing ◽  
Liver And Kidney ◽  
To Receive

Objective: The objective of this study is to preliminarily evaluate the efficacy of the combination of baicalein and docetaxel on non-small cell lung cancer (NSCLC) in vivo. Methods: The subcutaneous model was established by inoculation of A549 cells, and then these tumor-bearing mice were randomly assigned to eight groups to receive normal saline (NS) as control, baicalein alone, Taxotere[Formula: see text] (docetaxel injection) alone or the combination of baicalein and Taxotere[Formula: see text]. The effect of the combination treatment was evaluated by [Formula: see text] value. Tumors were harvested for TUNEL and CD31 immunohistochemical staining and important organs for H&E staining. Results: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg significantly reduced tumor weight and inhibited the growth rate of tumor, displaying the additive effect indicated by the [Formula: see text] value. Increased apoptosis and decreased tumor angiogenesis also provided pathological evidence. Additionally, baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg did not increase toxicity in lung, liver and kidney. Conclusion: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg additively inhibits the growth of NSCLC in vivo, and the mechanism underlying remains to be discovered.

scholarly journals Interferon Consensus Sequence-Binding Protein 8, a Tumor Suppressor, Suppresses Tumor Growth and Invasion of Non-Small Cell Lung Cancer by Interacting with the Wnt/β-Catenin Pathway

2018 ◽  
Vol 51 (2) ◽  
pp. 961-978 ◽  
Author(s):  
Lin Ye ◽  
Tingxiu Xiang ◽  
Jing Zhu ◽  
Dairong Li ◽  
Qin Shao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Consensus Sequence ◽  
Three Dimensional ◽  
Small Cell ◽  
Immunofluorescence Staining ◽  
Small Cell Lung

Background/Aims: Interferon consensus sequence-binding protein 8 (IRF8) belongs to a family of interferon (IFN) regulatory factors that modulates various important physiological processes including carcinogenesis. As reported by others and our group, IRF8 expression is silenced by DNA methylation in both human solid tumors and hematological malignancies. However, the role of IRF8 in lung carcinoma remains elusive. In this study, we determined IRF8 epigenetic regulation, biological functions, and the signaling pathway involved in non-small cell lung cancer (NSCLC). Methods: IRF8 expression were determined by Q- PCR. MSP and A+T determined promotor methylation. MTS, clonogenic, Transwell assay, Flow cytometry, three-dimensional culture and AO/EB stain verified cell function. In vivo tumorigenesis examed the in vivo effects. By Chip-QPCR, RT-PCR, Western blot and Immunofluorescence staining, the mechanisms were studied. Results: IRF8 was significantly downregulated in lung tumor tissues compared with adjacent non-cancerous tissues. Furthermore, methylation-specific PCR analyses revealed that IRF8 methylation in NSCLC was a common event, and demethylation reagent treatment proved that downregulation of IRF8 was due to its promoter CpG hypermethylation. Clinical data showed that the IRF8 methylation was associated with tumor stage, lymph node metastasis status, patient outcome, and tumor histology. Exogenous expression of IRF8 in the silenced or downregulated lung cancer cell lines A549 and H1299 at least partially restored the sensitivity of lung cancer cells to apoptosis, and arrested cells at the G0/G1 phase. Cell viability, clonogenicity, and cell migration and invasive abilities were strongly inhibited by restored expression of IRF8. A three-dimensional culture system demonstrated that IRF8 changed the cells to a more spherical phenotype. Moreover, ectopic expression of IRF8 enhanced NSCLC chemosensitivity to cisplatin. Furthermore, as verified by Chip-qPCR, immunofluorescence staining, and western blotting, IRF8 bound to the T-cell factor/lymphoid enhancer factor (TCF /LEF) promoter, thus repressing β-catenin nuclear translocation and its activation. IRF8 significantly disrupted the effects of Wnt agonist, bml284, further suggesting its involvement in the Wnt/β-catenin pathway. Conclusion: IRF8 acted as a tumor suppressor gene through the transcriptional repression of β-catenin-TCF/LEF in NSCLC. IRF8 methylation may serve as a potential biomarker in NSCLC prognosis.

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