scholarly journals Immunomodulatory Protein from Nectria haematococca Induces Apoptosis in Lung Cancer Cells via the P53 Pathway

2019 ◽  
Vol 20 (21) ◽  
pp. 5348 ◽  
Author(s):  
Jing-Jing Wang ◽  
Yan Wang ◽  
Lizhen Hou ◽  
Fengjiao Xin ◽  
Bei Fan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Wide Spectrum ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Pcr Analysis ◽  
Nectria Haematococca ◽  
Metabolic Pathway Analysis ◽  
P53 Expression ◽  
Immunomodulatory Protein ◽  
Mannose Metabolism

Our previous research has shown that a fungal immunomodulatory protein from Nectria haematococca (FIP-nha) possesses a wide spectrum of anti-tumor activities, and FIP-nha induced A549 apoptosis by negatively regulating the PI3K/Akt signaling pathway based on comparative quantitative proteomics. This study further confirmed that the anti-lung cancer activity of FIP-nha was significantly stronger than that of the reported LZ-8 and FIP-fve. Subsequently, 1H NMR-based metabolomics was applied to comprehensively investigate the underlying mechanism, and a clear separation of FIP-nha-treated and untreated groups was achieved using pattern recognition analysis. Four potential pathways associated with the anti-tumor effect of FIP-nha on A549 cells were identified, and these were mainly involved in glycolysis, taurine and hypotaurine metabolism, fructose and mannose metabolism, and glycerolipid metabolism. Metabolic pathway analysis demonstrated that FIP-nha could induce A549 cell apoptosis partly by regulating the p53 inhibition pathway, which then disrupted the Warburg effect, as well as through other metabolic pathways. Using RT-PCR analysis, FIP-nha-induced apoptosis was confirmed to occur through upregulation of p53 expression. This work highlights the possible use of FIP-nha as a therapeutic adjuvant for lung cancer treatment.

scholarly journals MiR-107 inhibits proliferation of lung cancer cells through regulating TP53 regulated inhibitor of apoptosis 1 (TRIAP1)

2017 ◽  
Vol 12 (1) ◽  
pp. 200-205 ◽  
Author(s):  
Bing Wang ◽  
Zhanjie Zuo ◽  
Fang Lv ◽  
Liang Zhao ◽  
Minjun Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Pcr Analysis ◽  
Aberrant Expression ◽  
Small Interference Rna ◽  
Qrt Pcr

AbstractAimsAccumulating evidence indicates that aberrant expression of miR-107 plays a crucial role in cancers. This study aims to display the function of miR-107 and its novel target genes in the progression of lung cancer.Methods and MaterialMiR-107 or miR-107 inhibitor was transfected into lung cancer cells A549. The levels of miR-107 and TP53 regulated inhibition of apoptosis 1 (TRIAP1) were examined by quantitative real-time Polymerase Chain Reaction (qRT-PCR) analysis and Western Blot. Functionally, MTT and colony formation assays were carried out to test the effect of miR-107 inhibitor and/or small interference RNA (siRNA) targeting TRIAP1 mRNA on proliferation of lung cancer cells. Levels of miR-107 or TRIAP1 were detected in clinical lung cancer samples by using qRT-PCR analysis.ResultsQRT-PCR analysis revealed that miR-107 inhibitor or miR-107 was successfully transfected into A549 cells. Western Blot indicated that miR-107 decreased the expression of TRIAP1 protein in the cells. In contrast, miR-107 inhibitor augmented the levels of TRIAP1 protein. Functionally, miR-107 inhibitor remarkably suppressed A549 cell proliferation, whereas, TRIAP1 siRNAs could abrogate the miR-107 inhibitor-induced proliferation of cells. Then, we validated that TRIAP1 was increased in clinical lung cancer samples. MiR-107 expression was negatively related to TRIAP1 expression in clinical lung cancer samples.ConclusionsMiR-107 suppresses cell proliferation by targeting TRIAP1 in lung cancer. Our finding allows new insights into the mechanisms of lung cancer that is mediated by miR-107.

scholarly journals Cytotoxic Effects of Flubendazole in Human Lung Cancer Cell Line A549

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Elham Hoveizi ◽  
Fatemeh Fakharzadeh Jahromi
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Human Lung ◽  
A549 Cells ◽  
Beclin 1 ◽  
Human Lung Cancer ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Acridine Orange Staining

Background: The development of effective anticancer drugs is a significant health issue. Previous studies showed that members of the benzimidazole family have anticancer effects on several cancers Objectives: The present study investigated the cytotoxic effect of flubendazole on A549 human lung cancer cells. Methods: The A549 cells were treated with flubendazole at 1, 2, 5, and 10 µM concentrations for three days. Cell viability was measured by the MTT assay and Acridine orange staining. Also, the expressions of P62 and Beclin -1 were analyzed by qRT-PCR analysis. Results: Cell viability of A549 cells, in a concentration-dependent manner, showed significant differences between the treatment and control groups, and the IC50 value was determined to be 2 µM. Also, flubendazole reduced the expression of P62 and increased the expression of Beclin 1 in treated cells. Conclusions: Flubendazole induces cell death in A549 cells in a dose and time-dependent manner and can offer new factors in lung cancer therapeutic strategies.

scholarly journals Low expression of miR-192 in NSCLC and its tumor suppressor functions in metastasis via targeting ZEB2

2016 ◽  
Vol 11 (1) ◽  
pp. 293-297 ◽  
Author(s):  
Zhang Yunxia ◽  
Dong Hongying
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Real Time ◽  
Real Time Pcr ◽  
Ectopic Expression ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Invasion Assays

AbstractObjectivesLung cancer is the leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) accounting for more than 80% of all lung cancer cases. The aim of this study was to investigate the function and underlying mechanism of microRNA-192 (miR-192) in metastasis of NSCLC cells.MethodsReal-time PCR was applied to quantify the expression of miR-192 in NSCLC tissues and cell lines, matched with their corresponding controls. The biological roles of miR-192 were studied in NSCLC cells using the wound healing and trans well invasion assays. Real-time PCR and western blot were used to evaluate the regulation of ZEB2 by miR- 192.ResultsMiR-192 was expressed significantly lower in NSCLC tissues/cells when compared with controls. Ectopic expression of miR-192 strongly inhibited cell migration and invasion in NSCLC A549 cells. Further investigation revealed ZEB2, an EMT regulator, was one of the downstream targets regulated by miR-192.ConclusionThese results suggested that miR-192 inhibits the metastasis of NSCLC cells by targeting ZEB2, and thus is an important tumor suppressor.

scholarly journals Transcriptome Analysis of Phycocyanin-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer A549 Cell Growth

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 511 ◽  
Author(s):  
Shuai Hao ◽  
Shuang Li ◽  
Jing Wang ◽  
Lei Zhao ◽  
Yan Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transcriptome Analysis ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Protein Interaction ◽  
Differential Genes

Phycocyanin (PC), derived from cyanobacteria and Spirulina cells, is a type of natural antineoplastic marine protein. It has been reported that phycocyanin exerts an antitumor function in non-small cell lung cancer (NSCLC) cells, but the underlying mechanism has not been elucidated. In this research, a transcriptome study was performed to investigate the regulatory mechanisms of phycocyanin on human NSCLC A549 cells. The survival rate and proliferation ability of A549 cells were markedly reduced by phycocyanin, along with abnormal morphologic changes. The transcriptome analysis showed that 2970 genes were differentially expressed after phycocyanin treatment in A549 cells, including 1431 down-regulated and 1539 up-regulated genes. Gene ontology and KEGG analysis suggested that some classical pathways, such as Wnt, NF-κB, and PI3K-AKT signaling, were significantly enriched. Strikingly, protein–protein interaction (PPI) analysis showed that ubiquitin-C (UBC) occupied the highest degree (the highest number of interactions) in differential genes, indicating that it might play a key role in the phycocyanin-mediated regulatory process in A549 cells. Moreover, qRT-PCR results showed consistent expression trends of differential genes with transcriptome analysis. Consequently, this study has provided a theoretical basis for regulation of phycocyanin in A549 cells, which lays a foundation for the treatment of NSCLC.

scholarly journals SOX2 Knockdown with Sirna Reverses Cisplatin Resistance in NSCLC by Regulating APE1 Signaling

2021 ◽  
Author(s):  
Taiyu Chen ◽  
Ji Zhou ◽  
Peng-cheng Li ◽  
Chun-han Tang ◽  
Fang Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Binding Sites ◽  
Colony Formation ◽  
Cisplatin Resistance ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Sox2 Expression ◽  
Reporter Assays ◽  
Nsclc Patients

Abstract Objective: SOX2 is related to drug resistance in many types of cancer, including lung cancer, but the underlying mechanism is still not fully understood. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC).Methods: Cisplatin-resistant NSCLC A549/CDDP cells, parental A549 cells and NCI-H460 cells were selected for experiments. The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR (qPCR), immunohistochemistry (IHC), and luciferase reporter assays were used to investigate the underlying mechanism of SOX2. Kaplan-Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression levels and patient survival.Results: A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP cells was higher than that in A549 cells. Knockdown of SOX2 in A549/CDDP cells induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by small hairpin RNA against APE1 (shAPE1) in A549/CDDP cells. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP cells treated with SOX2 small-interfering RNA (siSOX2) alone or combined with CDDP compared with control cells. Meaningfully, SOX2 expression was variable in 45 advanced NSCLC patients, and patients with high expression of SOX2 survived longer than those with low expression of SOX2.Conclusion: siSOX2 overcomes cisplatin resistance in NSCLC by regulating APE1 signaling, providing a new therapeutic target for overcoming cisplatin resistance in NSCLC patients.

scholarly journals microRNA-1236-3p regulates DDP resistance in lung cancer cells

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Zhigang Wang ◽  
Limei Liu ◽  
Xiaofeng Guo ◽  
Chunmei Guo ◽  
Wenxia Wang
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Chemotherapy Resistance ◽  
A549 Cells ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Expression Level ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Direct Target Gene

AbstractLung cancer is a malignant tumor leading to the most cancer-related deaths worldwide. The treatment efficiency of lung cancer remains poor mainly due to chemotherapy drug resistance, including cisplatin. MicroRNAs (miRNAs) are closely related to chemotherapy resistance of tumor cells. Here, we illustrated the underlying mechanism of miR-1236-3p on the DDP resistance in lung cancer cells. In this study, we found that the expression level of miR-1236-3p was significantly decreased in lung cancer tissues and A549 cell line. In addition, the half maximal inhibitory concentration (IC50) of DDP in A549 cells was significantly lower than that in A549/DDP cells, while the expression level of miR-1236-3p was prominently down-regulated in A549/DDP cells. Combining the online tool TargetScan and a dual-luciferase reporter assay, tumor protein, translationally-controlled 1 (TPT1) was proved to be the direct target gene of miR-1236-3p. The MTT and flow cytometry assays demonstrated that up-regulation of miR-1236-3p could markedly inhibit A549/DDP cell proliferation but promote apoptosis, which could be significantly reversed by pcDNA3.1-TPT1 plasmids. Finally, we further demonstrated that miR-1235-3p could restrain the expression levels of TPT1, Pim-3, phosphate-Bcl-2-associated death promoter (p-BAD) and B-cell lymphoma-extra large (Bcl-XL) in A549/DDP cells, while the inhibition could be reversed by pcDNA3.1-TPT1 as well. In a word, our study demonstrated that miR-1236-3p could reverse DDP resistance by modulation of TPT1 gene and inhibition of Pim-3 signaling pathway in lung cancer cells.

scholarly journals Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tianze Zhang ◽  
Yongchao Li ◽  
Ruidong Zhu ◽  
Pengcheng Song ◽  
Youlei Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Nsclc Patients

Objective. To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). Methods. The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. Results. p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. Conclusions. Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

scholarly journals Fungal Immunomodulatory Protein from Nectria haematococca Suppresses Growth of Human Lung Adenocarcinoma by Inhibiting the PI3K/Akt Pathway

2018 ◽  
Vol 19 (11) ◽  
pp. 3429 ◽  
Author(s):  
Yingying Xie ◽  
Shuying Li ◽  
Lei Sun ◽  
Shujun Liu ◽  
Fengzhong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Cell Cycle Arrest ◽  
Cyclin B1 ◽  
Common Disease ◽  
Nectria Haematococca ◽  
Cycle Arrest ◽  
Fungal Immunomodulatory Protein ◽  
Immunomodulatory Protein

Lung cancer is a common disease that is associated with poor prognosis. Fungal immunomodulatory protein from Nectria haematococca (FIP-nha) has potential as a lung cancer therapeutic; as such, illuminating its anti-tumor mechanism is expected to facilitate novel treatment options. Here, we showed that FIP-nha affects lung adenocarcinoma growth ex vivo and in vivo. Comparative quantitative proteomics showed that FIP-nha negatively regulates PI3K/Akt signaling and induces cell cycle arrest, autophagy, and apoptosis. We further demonstrated that FIP-nha suppresses Akt phosphorylation, leading to upregulation of p21 and p27 and downregulation of cyclin B1, cyclin D1, CDK2, and CDK4 expression, ultimately resulting in G1/S and G2/M cell cycle arrest. Meanwhile, FIP-nha-induced PI3K/Akt downregulation promotes A549 apoptosis by increasing the expression ratio of Bax/Bcl-2 and c-PARP and autophagy by decreasing the phosphorylation of mTOR. Thus, we comprehensively revealed the anti-tumor mechanism of FIP-nha, which inhibits tumor growth by modulating PI3K/Akt-regulated cell cycle arrest, autophagy, and apoptosis, and provided the basis for further application of fungal immunomodulatory proteins, especially FIP-nha.

scholarly journals Sevoflurane induces lung cancer cell apoptosis via inhibition of the expression of miRNA155 gene

2021 ◽  
Vol 20 (1) ◽  
pp. 69-74
Author(s):  
Huaizhao Wang ◽  
Bin Wang ◽  
Jingyan Jing ◽  
Na Li
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Lung Cancer Cells ◽  
Control Group ◽  
Sevoflurane Group ◽  
Lung Adenocarcinoma A549

Purpose: To determine the apoptotic effect of sevoflurane on lung cancer cells, and the underlying mechanism of action.Methods: Lung adenocarcinoma A549 cells were cultured for 24 h and divided into control group, 1% sevoflurane group and 3% sevoflurane group. The two levels of sevoflurane were provided through a gas monitor connected to each of the sevoflurane groups. The control group was not treated. Flow cytometry was used to analyze A549 cell apoptosis, while qRT-PCR was used for assay of the levels of miRNA155 in A549 cells. The protein expression of Bcl-2 was determined with immunoblotting. The percentage of apoptosis and levels of miRNA155 and Bcl-2 in the two cell lines were compared.Results: Significant differences in miRNA146a level were seen between the 3 % sevoflurane and control groups at 3 h. There was higher apoptosis in the 3 % sevoflurane group, relative to control, but miRNA155 levels in the 3 % sevoflurane group were generally less than that of the control (p < 0.05). There was lower Bcl-2 content in the 3 % sevoflurane group than in control group (p < 0.05).Conclusion: Sevoflurane exerts strong apoptotic and anti-proliferative effects on lung adenocarcinoma A549 cells via a mechanism which may be related to the downregulation of miRNA155, thereby inhibiting the expression of anti-apoptotic protein Bcl-2. This provides a new direction for research on anti-lung adenocarcinoma drugs. Keywords: Sevoflurane, Lung cancer cells, Apoptosis, Inhibition, miRNA155, Expression, Induction

Regulatory Effects of Siegesbeckia glabrescens on Non-Small Cell Lung Cancer Cell Proliferation and Invasion

2014 ◽  
Vol 42 (02) ◽  
pp. 453-463 ◽  
Author(s):  
Ha Neul Lee ◽  
Ji-Hye Joo ◽  
Joa Sub Oh ◽  
Shin Wook Choi ◽  
Dong-Wan Seo
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Ethanol Extract ◽  
Small Cell ◽  
Small Cell Lung ◽  
P53 Expression ◽  
Proliferation And Invasion

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70S6K as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70S6K. In contrast, in H1299 cells the inactivation of p38MAPK appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC.

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