Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells

Zhang, Quan; Zhu, Hancheng; Xu, Xiaojun; Li, Lingyu; Tan, Haidong; Cai, Xiaoyao

doi:10.1016/j.bbrc.2015.07.130

Cited by 48 publications

(24 citation statements)

References 20 publications

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“…Three pathways (PI3K-Akt signaling pathway, TGF-beta signaling pathway and Hippo signaling pathway) were previously reported to be involved in NSCLC development and progression. As reported, the PI3K-Akt signaling pathway was related to NSCLC cell proliferation, apoptosis and autophagy [27–29]. The TGF-beta signaling pathway could be associated with the NSCLC cell DNA damage response, radiation sensitivity, viability and invasion capacity [30, 31].…”

Section: Resultsmentioning

confidence: 98%

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Zhang

Dang

et al. 2016

Cancer Cell Int

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BackgroundLong noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown.MethodsHOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve.ResultsAmong the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663–0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906–0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = −0.124, P = 0.048) and lung adenocarcinoma (r = −0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA.Conclus...

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Section: Resultsmentioning

confidence: 98%

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Zhang

Dang

et al. 2016

Cancer Cell Int

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“…AKT may inhibit cell apoptosis and activate effector molecules, including Bad, caspase-9, FKHR1 and nuclear factor-κB. AKT also participates in cell cycle regulation (it is clarified at present that AKT upregulates c-myc expression by increasing its transcription), promotes tumor angiogenesis (AKT may activate nitric oxide synthase and thereby stimulates the growth and proliferation of endothelial cells, increases vascular permeability and promotes angiogenesis following angiectasis, which provides sufficient nutrition for tumor cells) and enhances cell invasion and metastasis (11,29). In addition, it was revealed that the PI3K inhibitor suppresses the PI3K/AKT signaling pathway and reversed the anticancer effects of miR-145 upregulation in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

“…A ligand binds with the N-terminal extracellular domain of EGFR to form a homodimer or heterodimer, which phosphorylates the tyrosine residue in the cell, thereby activating the downstream signaling pathways. These signaling pathways include the RAS/RAF/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway and the signal transducer and activator of transcription 3/5 signal transduction pathway (11). Ligand binding ultimately results in a series of abnormal biological behaviors in tumor cells, including excessive proliferation and invasion, metastasis and angiogenesis (12).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑145 inhibits migration and induces apoptosis in human non‑small cell lung cancer cells through regulation of the EGFR/PI3K/AKT signaling pathway

Ding

et al. 2018

Oncol Rep

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In the present study, the therapeutic effects and the underlying molecular mechanisms of microRNA (miR)‑145 were investigated in non‑small cell lung cancer (NSCLC) cells. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to examine miR‑145 expression. An MTT assay and flow cytometry were used to investigate cell proliferation and apoptosis, respectively. The protein expression of Bax, epidermal growth factor receptor (EGFR), phosphatidylinositol 3‑kinase (PI3K) and phosphorylated‑protein kinase B (AKT) was examined by western blot analysis. miR‑145 expression was downregulated in patients with NSCLC who were treated with chemotherapy. The downregulation of miR‑145 in A549 cells reduced lactate dehydrogenase (LDH) expression, apoptosis, caspase‑3/-9 levels and Bax protein expression, while it increased cell proliferation. Upregulation of miR‑145 in A459 cells increased LDH, apoptosis, caspase‑3/-9 levels and Bax protein expression, while it inhibited cell proliferation. The EGFR/PI3K/AKT signaling pathway was suppressed by miR‑145 upregulation in A549 cells and induced by miR‑145 downregulation. The EGFR inhibitor suppressed the EGFR/PI3K/AKT signaling pathway and increased the anticancer effects of miR‑145 upregulation in A549 cells. The PI3K inhibitor suppressed the PI3K/AKT signaling pathway and reversed the anticancer effects of miR‑145 upregulation in A549 cells. In conclusion, the present study demonstrated that miR‑145 regulates the EGFR/PI3K/AKT signaling pathway in patients with NSCLC.

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“…Sendai virus (SeV) is a prototypic member of the family Paramyxoviridae. It has been demonstrated that ultraviolet (UV)-inactivated SeV may exert anticancer effects by inducing cancer-selective apoptosis, autophage and anticancer immune responses (Kurooka and Kaneda 2007;Zhang et al 2015;Li et al 2017). However, the molecular mechanisms underlying its anti-tumor effects have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of inactivated Sendai virus strain Tianjin on human osteosarcoma HOS cells

Sun²,

Shi³

2019

gpb

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Ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) has been proved to have antitumor effects in many kinds of tumor cells. Here, we investigated the anticancer properties of UV-Tianjin on human osteosarcoma (HOS) cells and the underlying molecular mechanism. Apoptosis, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were determined by flow cytometry analysis. The expression levels of apoptosis-related proteins were tested by Western blotting. The results showed that UV-Tianjin concentration-dependently induced apoptosis in HOS cells. UV-Tianjin-induced apoptosis was mediated by the mitochondrial pathway, which was confirmed by mitochondrial dysfunction, downregulation of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL) and myeloid cell leukemia-1 (Mcl-1), upregulation of Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), as well as the cleavage of caspase-9 and caspase-3. Further analysis showed that UV-Tianjin augmented the phosphorylation of c-Jun N-terminal kinase, the extracellular-regulated kinase and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, as well as the generation of ROS. Moreover, UV-Tianjin-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor. Taken together, our results indicated that UV-Tianjin exerts antitumor effects by inducing mitochondria-dependent apoptosis involving ROS generation and MAPK pathway in human osteosarcoma HOS cells.

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Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells

Cited by 48 publications

References 20 publications

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

MicroRNA‑145 inhibits migration and induces apoptosis in human non‑small cell lung cancer cells through regulation of the EGFR/PI3K/AKT signaling pathway

Anticancer effect of inactivated Sendai virus strain Tianjin on human osteosarcoma HOS cells

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