scholarly journals Targeted Nanoparticles Harboring Jasmine-Oil-Entrapped Paclitaxel for Elimination of Lung Cancer Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1019
Author(s):  
Shira Engelberg ◽  
Yuexi Lin ◽  
Yehuda G. Assaraf ◽  
Yoav D. Livney
Keyword(s):  
Lung Cancer ◽  
Targeted Drug Delivery ◽  
A549 Cells ◽  
Average Diameter ◽  
Delivery Systems ◽  
Small Cell Lung ◽  
Targeted Nanoparticles ◽  
Ic50 Value ◽  
Residual Amount ◽  
Human Nsclc

Selectively targeted drug delivery systems are preferable chemotherapeutic platforms, as they specifically deliver the drug cargo into tumor cells, while minimizing untoward toxic effects. However, these delivery systems suffer from insufficient encapsulation efficiency (EE), encapsulation capacity (EC), and premature drug release. Herein, we coencapsulated paclitaxel (PTX) and Jasmine oil (JO) within PEG-PCL nanoparticles (NPs), with an average diameter < 50 nm, selectively targeted to non-small cell lung cancer (NSCLC) cells, via S15-aptamer (APT) decoration. JO was selected as an “adhesive” oily core to enhance PTX entrapment, as JO and PTX share similar hydrophobicity and terpenoid structure. JO markedly enhanced EE of PTX from 23% to 87.8% and EC from 35 ± 6 to 74 ± 8 µg PTX/mg PEG-PCL. JO also markedly increased the residual amount of PTX after 69 h, from 18.3% to 65%. Moreover, PTX cytotoxicity against human NSCLC A549 cells was significantly enhanced due to the co-encapsulation with JO; the IC50 value for PTX encapsulated within JO-containing APT-NPs was 20-fold lower than that for APT-NPs lacking JO. Remarkably, JO-containing APT-NPs displayed a 6-fold more potent cell-killing, relatively to the free-drug. Collectively, these findings reveal a marked synergistic contribution of JO to the cytotoxic activity of APT-NP-based systems, for targeted PTX delivery against NSCLC, which may be readily applied to various hydrophobic chemotherapeutics.

scholarly journals MicroRNA-4651 targets bromodomain-containing protein 4 to inhibit non-small cell lung cancer cell growth

2019 ◽  
Author(s):  
Jiangnan Zheng ◽  
Lingyun Dong ◽  
Yan Zhang ◽  
Shang Cai ◽  
Xiaoyun Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
A549 Cells ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
And Migration ◽  
Human Nsclc ◽  
Proliferation And Migration

Abstract Background: Bromodomain-containing protein 4 (BRD4) overexpression in non-small cell lung cancer (NSCLC) is important for cancer cell progression. The aim of the present study is to silence BRD4 through expression of its targeted microRNAs in NSCLC cells. Methods: Expression of BRD4 and its targeting miRNA, microRNA-4651 (miR-4651), was tested by qPCR and Western blotting assays. Genetic strategies were utilized to exogenously alter miR-4651 expression. NSCLC cell growth, proliferation and migration were tested. Results: miR-4651 selectively targets and negatively regulates BRD4 in A549 and primary human NSCLC cells. The Ago-2 immunoprecipitation experiments further confirmed that miR-4651 directly binds to BRD4 mRNA. Significantly, in A549 cells and primary NSCLC cells ectopic overexpression of miR-4651 downregulated BRD4’s 3-UTR activity and its expression, both were however elevated with miR-4651 inhibition. Functional studies demonstrated that NSCLC cell growth, proliferation and migration were significantly inhibited with miR-4651 overexpression, but enhanced with miR-4651 inhibition. BRD4 re-expression, by an 3’-UTR mutant BRD4, reversed miR-4651 overexpression-induced inhibitions on A549 cells. Additionally, miR-4651 overexpression or inhibition failed to affect the functions of BRD4-KO A549 cells. In vivo, miR-4651-overexpressed A549 xenografts grew significantly slower than control A549 xenografts in severe combined immunodeficient mice. At last we show that miR-4651 is downregulated in human NSCLC tissues, correlating with BRD4 elevation. Conclusions: miR-4651 targets BRD4 to inhibit NSCLC cell growth in vitro and in vivo.

scholarly journals MicroRNA-4651 targets bromodomain-containing protein 4 to inhibit non-small cell lung cancer cell growth

2019 ◽  
Author(s):  
Jiangnan Zheng ◽  
Lingyun Dong ◽  
Yan Zhang ◽  
Shang Cai ◽  
Xiaoyun Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
A549 Cells ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
And Migration ◽  
Human Nsclc ◽  
Proliferation And Migration

Abstract Background: Bromodomain-containing protein 4 (BRD4) overexpression in non-small cell lung cancer (NSCLC) is important for cancer cell progression. The aim of the present study is to silence BRD4 through expression of its targeted microRNAs in NSCLC cells. Methods: Expression of BRD4 and its targeting miRNA, microRNA-4651 (miR-4651), was tested by qPCR and Western blotting assays. Genetic strategies were utilized to exogenously alter miR-4651 expression. NSCLC cell growth, proliferation and migration were tested. Results: miR-4651 selectively targets and negatively regulates BRD4 in A549 and primary human NSCLC cells. The Ago-2 immunoprecipitation experiments further confirmed that miR-4651 directly binds to BRD4 mRNA. Significantly, in A549 cells and primary NSCLC cells ectopic overexpression of miR-4651 downregulated BRD4’s 3-UTR activity and its expression, both were however elevated with miR-4651 inhibition. Functional studies demonstrated that NSCLC cell growth, proliferation and migration were significantly inhibited with miR-4651 overexpression, but enhanced with miR-4651 inhibition. BRD4 re-expression, by an 3’-UTR mutant BRD4, reversed miR-4651 overexpression-induced inhibitions on A549 cells. Additionally, miR-4651 overexpression or inhibition failed to affect the functions of BRD4-KO A549 cells. In vivo, miR-4651-overexpressed A549 xenografts grew significantly slower than control A549 xenografts in severe combined immunodeficient mice. At last we show that miR-4651 is downregulated in human NSCLC tissues, correlating with BRD4 elevation. Conclusions: miR-4651 targets BRD4 to inhibit NSCLC cell growth in vitro and in vivo.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

2020 ◽  
Vol 20 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Le-Le Zhang ◽  
Han Bao ◽  
Yu-Lian Xu ◽  
Xiao-Ming Jiang ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Immunofluorescence Assay ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

scholarly journals Aptamer-modified polymer nanoparticles for targeted drug delivery

2016 ◽  
Vol 17 (1-2) ◽  
Author(s):  
Julia Modrejewski ◽  
Johanna-Gabriela Walter ◽  
Imme Kretschmer ◽  
Evren Kemal ◽  
Mark Green ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Drug Delivery ◽  
Drug Delivery Systems ◽  
Mode Of Delivery ◽  
Delivery Systems ◽  
The Body ◽  
Lung Cancer Cells ◽  
Targeted Drug

AbstractThe purpose of this study was to develop a model system for targeted drug delivery. This system should enable targeted drug release at a certain tissue in the body. In conventional drug delivery systems, drugs are often delivered unspecifically resulting in unwarranted adverse effects. To circumvent this problem, there is an increasing demand for the development of intelligent drug delivery systems allowing a tissue-specific mode of delivery. Within this study, nanoparticles consisting of two biocompatible polymers are used. Because of their small size, nanoparticles are well-suited for effective drug delivery. The small size affects their movement through cell and tissue barriers. Their cellular uptake is easier when compared to larger drug delivery systems. Paclitaxel was encapsulated into the nanoparticles as a model drug, and to achieve specific targeting an aptamer directed against lung cancer cells was coupled to the nanoparticles surface. Nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), and nanotracking analysis (NTA). Also their surface charge was characterized from ζ-potential measurements. Their preparation was optimized and subsequently specificity of drug-loaded and aptamer-functionalized nanoparticles was investigated using lung cancer cells.

CELL LADEN ALGINATE/ALBUMIN HYDROGEL FIBERS FOR POTENTIAL SKIN TISSUE ENGINEERING APPLICATIONS

2018 ◽  
Vol 30 (06) ◽  
pp. 1850045
Author(s):  
Maria Grazia Cascone ◽  
Elisabetta Rosellini ◽  
Simona Maltinti ◽  
Andrea Baldassare ◽  
Luigi Lazzeri
Keyword(s):  
Tissue Engineering ◽  
A549 Cells ◽  
Average Diameter ◽  
Favorable Effect ◽  
Engineering Applications ◽  
Residual Amount ◽  
Spinning Process ◽  
Proliferation Ability ◽  
Alginate Fibers ◽  
Kinetics Of

Alginate hydrogel fibers are receiving a great attention for tissue engineering applications. However, an important limitation of alginate is that it does not provide cell adhesion motifs. In this work, albumin was blended with alginate to improve the compatibility of alginate fibers with cells. Cell laden alginate/albumin fibers, potentially usable for skin regeneration, were obtained through a spinning process, by extruding an alginate/albumin solution containing cells into a calcium chloride solution. Cell laden pure alginate fibers were prepared for comparison. Plain alginate and alginate/albumin fibers were also produced. Morphological, mechanical and functional properties of the produced fibers were investigated. In addition, the ability of the fibers to release albumin and to support the viability and growth of A549 cells embedded into them was studied. Fibers with a uniform shape and an average diameter within the range 550–570[Formula: see text][Formula: see text]m were produced. The water content was [Formula: see text]% for alginate fibers, and [Formula: see text]% for alginate/albumin fibers. Stress–strain tests showed, up to a strain value of 20%, the same Young’s modulus for the produced fibers, regardless of the presence of albumin. Overall, obtained results demonstrated that morphology, size, hydrophilicity and mechanical properties were not affected by albumin. Albumin was gradually released over a period of 4 days, with a residual amount (13%) remaining into the fibers. Viability test was carried out on A549 cells, laden inside alginate and alginate/albumin fibers, to evaluate cell proliferation ability. A favorable effect of albumin on the loaded cells was evidenced by a faster kinetics of growth.

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 Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Kinesin Superfamily

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

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