Effects of MALAT1 on proliferation and apo- ptosis of human non-small cell lung cancer A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy

2018 ◽  
Vol 22 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Jun Ma ◽  
Kaiming Wu ◽  
Kuanzhi Liu ◽  
Rong Miao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Tumor Xenograft ◽  
Small Cell Lung ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth

scholarly journals PPy@Fe3O4 Nanoparticles Inhibit Tumor Growth and Metastasis Through Chemodynamic and Photothermal Therapy in Non-small Cell Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Danruo Fang ◽  
Hansong Jin ◽  
Xiulin Huang ◽  
Yongxin Shi ◽  
Zeyu Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Photothermal Therapy ◽  
Synergistic Effects ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is considered to be a principal cause of cancer death across the world, and nanomedicine has provided promising alternatives for the treatment of NSCLC in recent years. Photothermal therapy (PTT) and chemodynamic therapy (CDT) have represented novel therapeutic modalities for cancer treatment with excellent performance. The purpose of this research was to evaluate the effects of PPy@Fe3O4 nanoparticles (NPs) on inhibiting growth and metastasis of NSCLC by combination of PTT and CDT. In this study, we synthesized PPy@Fe3O4 NPs through a very facile electrostatic absorption method. And we detected reactive oxygen species production, cell apoptosis, migration and protein expression in different groups of A549 cells and established xenograft models to evaluate the effects of PPy@Fe3O4 NPs for inhibiting the growth of NSCLC. The results showed that the PPy@Fe3O4 NPs had negligible cytotoxicity and could efficiently inhibit the cell growth and metastasis of NSCLC in vitro. In addition, the PPy@Fe3O4 NPs decreased tumor volume and growth in vivo and endowed their excellent MRI capability of observing the location and size of tumor. To sum up, our study displayed that the PPy@Fe3O4 NPs had significant synergistic effects of PTT and CDT, and had good biocompatibility and safety in vivo and in vitro. The PPy@Fe3O4 NPs may be an effective drug platform for the treatment of NSCLC.

scholarly journals Antitumor Activity of DFX117 by Dual Inhibition of c-Met and PI3Kα in Non-Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 627 ◽  
Author(s):  
Yanhua Fan ◽  
Huaiwei Ding ◽  
Donghwa Kim ◽  
Duc-Hiep Bach ◽  
Ji-Young Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pik3ca Mutation ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients.

scholarly journals Engineered exosomes loaded with miR-449a selectively inhibit the growth of homologous non-small cell lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen Zhou ◽  
Mingming Xu ◽  
Zhipeng Wang ◽  
Mingjun Yang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transfection Efficiency ◽  
Drug Carrier ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

AbstractAs an efficient drug carrier, exosome has been widely used in the delivery of genetic drugs, chemotherapeutic drugs, and anti-inflammatory drugs. As a genetic drug carrier, exosomes are beneficial to improve transfection efficiency and weaken side effects at the same time. Here, we use genetic engineering to prepare engineered exosomes (miR-449a Exo) that can actively deliver miR-449a. It was verified that miR-449a Exo had good homology targeting capacity and was specifically taken up by A549 cells. Moreover, miR-449a Exo had high delivery efficiency of miR-449a in vitro and in vivo. We demonstrated that miR-449a Exo effectively inhibited the proliferation of A549 cells and promoted their apoptosis. In addition, miR-449a Exo was found to control the progression of mouse tumors and prolong their survival in vivo. Our research provides new ideas for exosomes to efficiently and actively load gene drugs, and finds promising methods for the treatment of non-small cell lung cancer.

scholarly journals MicroRNA-421 confers paclitaxel resistance by binding to the KEAP1 3′UTR and predicts poor survival in non-small cell lung cancer

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Fu-Gang Duan ◽  
Mei-Fang Wang ◽  
Ya-Bing Cao ◽  
Dan Li ◽  
Run-Ze Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

Abstract MicroRNAs regulate post-transcriptional gene expression and play important roles in multiple cellular processes. In this study, we found that miR-421 suppresses kelch-like ECH-associated protein 1(KEAP1) expression by targeting its 3′-untranslated region (3′UTR). A Q-PCR assay demonstrated that miR-421 is overexpressed in non-small cell lung cancer (NSCLC), especially in A549 cells. Consistently, the level of miR-421 was higher in clinical blood samples from lung cancer patients than in those from normal healthy donors, suggesting that miR-421 is an important lung cancer biomarker. Interestingly, overexpression of miR-421 reduced the level of KEAP1 expression, which further promoted lung cancer cell migration and invasion, as well as inhibited cell apoptosis both in vivo and in vitro. Furthermore, knockdown of miR-421 expression with an antisense morpholino oligonucleotide (AMO) increased ROS levels and treatment sensitivity to paclitaxel in vitro and in vivo, indicating that high miR-421 expression may at least partly account for paclitaxel tolerance in lung cancer patients. To find the upstream regulator of miR-421, one of the candidates, β-catenin, was knocked out via the CRISPR/Cas9 method in A549 cells. Our data showed that inhibiting β-catenin reduced miR-421 levels in A549 cells. In addition, β-catenin upregulation enhanced miR-421 expression, indicating that β-catenin regulates the expression of miR-421 in lung cancer. Taken together, our findings reveal the critical role of miR-421 in paclitaxel drug resistance and its upstream and downstream regulatory mechanisms. Therefore, miR-421 may serve as a potential molecular therapeutic target in lung cancer, and AMOs may be a potential treatment strategy.

scholarly journals Qiyusanlong Formula Induces Autophagy in Non-Small-Cell Lung Cancer Cells and Xenografts through the mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yating Gao ◽  
Xinheng Wang ◽  
Qinjun Yang ◽  
Xiaole Wang ◽  
Xingxing Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Small Cell ◽  
Mtor Signaling Pathway ◽  
Small Cell Lung

Objective. Qiyusanlong (QYSL) formula has been used in the clinic for more than 20 years and has been proved to have pronounced efficacy in the treatment of non-small-cell lung cancer (NSCLC). This work aims to evaluate the molecular mechanism of QYSL formula action on NSCLC, specifically in relation to autophagy induction. Methods. In vitro, CCK-8 was used to detect the effect of QYSL serum on cell viability in A549 cells. In vivo, A549 cells were implanted subcutaneously in nude mice to establish a xenograft model. TUNEL staining was used to measure cell apoptosis and TEM to observe the autophagy-related morphological changes in vitro and in vivo. Western blotting, RT-qPCR, and immunofluorescence were used to measure autophagy-related proteins. In addition, rapamycin (an inhibitor of mTOR and inducer of autophagy) and MHY1485 (an activator of mTOR and inhibitor of autophagy) were used to determine whether QYSL-induced autophagy was regulated by the mTOR pathway. Results. QYSL serum inhibited the cell viability of A549 cells in a concentration‐dependent manner. In vivo, the QYSL formula inhibited xenograft growth. The QYSL formula promoted apoptosis in A549 cells and induced autophagosome formation in vitro and in vivo. In addition, the QYSL formula downregulated the expression of mTOR and p62, while it upregulated the expression of ATG-7 and Beclin-1 and increased the LC3-II/LC3-I ratio. QYSL serum inhibited p-mTOR in a similar manner to rapamycin while reducing the activating effects of MHY1485 on p-mTOR. Conclusion. The QYSL formula has anti-lung cancer effects and promotes autophagy through the mTOR signaling pathway.

scholarly journals Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model

2021 ◽  
Vol 9 ◽  
Author(s):  
Zi-Ning Lei ◽  
Qiu-Xu Teng ◽  
Pranav Gupta ◽  
Wei Zhang ◽  
Silpa Narayanan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Model ◽  
Xenograft Model ◽  
Small Cell ◽  
Tumor Xenograft ◽  
Small Cell Lung

Cabozantinib (CBZ) is a small molecule tyrosine kinase receptor inhibitor, which could also inhibit the ABCG2 transporter function. Therefore, CBZ could re-sensitize cancer cells that are resistant to ABCG2 substrate drugs including topotecan (TPT). However, its reversal effect against TPT resistance has not been tested in a TPT-induced resistant cancer model. In this study, a new TPT selected human non-small cell lung cancer (NSCLC)-resistant cell model NCI-H460/TPT10 with ABCG2 overexpression and its parental NCI-H460 cells were utilized to investigate the role of CBZ in drug resistance. The in vitro study showed that CBZ, at a non-toxic concentration, could re-sensitize NCI-H460/TPT10 cells to TPT by restoring intracellular TPT accumulation via inhibiting ABCG2 function. In addition, the increased cytotoxicity by co-administration of CBZ and TPT may be contributed by the synergistic effect on downregulating ABCG2 expression in NCI-H460/TPT10 cells. To further verify the applicability of the NCI-H460/TPT10 cell line to test multidrug resistance (MDR) reversal agents in vivo and to evaluate the in vivo efficacy of CBZ on reversing TPT resistance, a tumor xenograft mouse model was established by implanting NCI-H460 and NCI-H460/TPT10 into nude mice. The NCI-H460/TPT10 xenograft tumors treated with the combination of TPT and CBZ dramatically reduced in size compared to tumors treated with TPT or CBZ alone. The TPT-resistant phenotype of NCI-H460/TPT10 cell line and the reversal capability of CBZ in NCI-H460/TPT10 cells could be extended from in vitro cell model to in vivo xenograft model. Collectively, CBZ is considered to be a potential approach in overcoming ABCG2-mediated MDR in NSCLC. The established NCI-H460/TPT10 xenograft model could be a sound clinically relevant resource for future drug screening to eradicate ABCG2-mediated MDR in NSCLC.

scholarly journals Effects of Laminaria Japonica Polysaccharides on the Survival of Non-Small-Cell Lung Cancer A549 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Mengxing Yao ◽  
XiaoJun Qian ◽  
Houying Qin
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung

Objective. To investigate the effect of Laminaria japonica polysaccharides (LJP) on the survival of non-small-cell lung cancer (NSCLC) A549 cells and its mechanism. Methods. In vitro: the cells were randomly divided into control group, LJP (5 mg/ml) group, LJP (10 mg/ml) group, and LJP (20 mg/ml) group. After corresponding treatment, the survival rate and the expression of proteins related to proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and signaling pathway were detected by CCK8 assay and Western blot, respectively. In vivo: a xenograft model was established to detect the tumor volume and mass and the expression of the above pathway proteins. Results. Compared with the control group, LJP decreased the survival rate of A549 cells (P<0.05), inhibited the protein expression of Ki67 and PCNA (P<0.05), downregulated the expression of Bcl-2 while upregulated the expression of Bax, cl-caspase-3, and cl-caspase-9 (P<0.05), upregulated the expression of E-cadherin, downregulated the expression of vascular endothelial growth factor (VEGF) and N-cadherin (P<0.05), and downregulated β-catenin, transcription factor-4 (TCF4), and c-Myc protein expression levels (P<0.05). In vivo: LJP decreased the volume and mass of the xenograft tumors and downregulated β-catenin, TCF4, and c-Myc protein expression levels compared with the control group (P<0.05). Conclusion. LJP can inhibit the survival of non-small-cell lung cancer A549 cells in vitro, and its mechanism is related to the inhibition of activation of β-catenin/TCF4 pathway activation.

scholarly journals Baicalein Inhibits Orthotopic Human Non-Small Cell Lung Cancer Xenografts via Src/Id1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhengxiao Zhao ◽  
Baojun Liu ◽  
Jing Sun ◽  
Linwei Lu ◽  
Lumei Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Non-small cell lung cancer (NSCLC) is one of the most lethal cancers worldwide. Inhibitor of differentiation 1 (Id1) is the member mostly linked to tumorigenesis in Id family and a potential molecular target in cancer therapy. In the current study, we established an orthotopic lung cancer model by injecting athymic nude mice with A549 cells and evaluated the antitumor effect of baicalein and expression of Id1-related proteins in vivo and in vitro. Micro-CT images showed that tumor volume in baicalein group was significantly reduced. Western blot analysis revealed that baicalein suppressed the expression of Id1 protein, epithelial-to-mesenchymal transition (EMT) related molecules (N-Cadherin, vimentin), and angiogenesis related protein (VEGF-A), accompanied by upregulation of epithelial markers (such as E-cadherin). In addition, phosphorylation of upstream molecular Src was significantly restrained after baicalein treatment. This study firstly demonstrates that baicalein inhibits tumor growth in orthotopic human NSCLC xenografts via targeting Src/Id1 pathway.

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