BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

Wang, Xingchun; Li, Minjie; Hu, Mengyao; Wei, Ping; Zhu, Wenhe

doi:10.3892/or.2017.5508

Cited by 33 publications

(27 citation statements)

References 42 publications

(42 reference statements)

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“…In the present study, it was demonstrated that Ep3 deficiency was involved in the regulation of cell viability, migration, invasion and apoptosis of A549 cells, and the underlying molecular mechanisms were investigated further. A number of studies have reported that TGF-β/Smad signaling is an important pathway in the progression of NSCLC ( 31 – 33 ), therefore whether TGF-β/Smad signaling mediated the roles of Ep3 was further investigated in A549 cells. The expression of pathway-associated proteins was evaluated using western blotting.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Ep3 attenuates migration and promotes apoptosis of non‑small cell lung cancer cells via suppression of TGF‑β/Smad signaling

Li¹,

Lv²,

Yan³

2018

Oncol Lett

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Non-small cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. Prostaglandin E2 (PGE2) regulates various biological processes, including invasion, proliferation and apoptosis. E-prostanoid 3 (Ep3) is a PGE2 receptor, and the functional role of Ep3 in the progression of NSCLC remains unresolved. The present study investigated the effects of Ep3 in A549 cells and explored the underlying molecular mechanisms. The results revealed that the mRNA and protein expression levels of Ep3 were significantly upregulated in NSCLC tissues and A549 cells. Pharmacological inhibition of Ep3 or RNA interference against Ep3 attenuated the cell viability, migration and invasion, and promoted apoptosis in A549 cells. Ep3 deficiency also decreased the expression of transforming growth factor (TGF)-β, phosphorylated (p)-Smad2 and p-Smad3. The transfection of TGF-β overexpression plasmids reversed the effects of Ep3 deficiency on the cell viability and apoptosis in A549 cells. Finally, an in vivo experiment revealed that Ep3-siRNA transfection strongly reduced the tumor growth and tumor volume. The Ep3-siRNA transfection also inhibited tumor metastasis via suppression of the expression of metastasis-associated proteins. Taken together, these findings indicate that inhibition of Ep3 attenuates the viability and migration, and promotes the apoptosis of NSCLC through suppression of the TGF-β/Smad signaling pathway. Targeting of the Ep3/TGF-β/Smad signaling pathway may be a novel therapeutic strategy for the prevention and treatment of NSCLC.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Ep3 attenuates migration and promotes apoptosis of non‑small cell lung cancer cells via suppression of TGF‑β/Smad signaling

Li¹,

Lv²,

Yan³

2018

Oncol Lett

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“…Beta-sitosterol (β-sitosterol) induced G0/G1 cell cycle arrest and inhibited cell proliferation in A549 cells. These results indicate that beta-sitosterol may serve as novel targets for the treatment of NSCLC [40]. Bio-assay guided fractionation showed the presence of phytosteols (β-sitosterol) which significantly inhibited the growth of A549 cells and promoted apoptosis alone or in combination.…”

Section: Constructing the Network Of Herb-ingredient-target-lc Therapmentioning

confidence: 77%

Network Pharmacology Approach Reveals the Potential Immune Function Activation and Tumor Cell Apoptosis Promotion of Xia Qi Decoction in Lung Cancer

Zhang

Wang

2019

Medical Sciences

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As the leading cause of cancer death worldwide, lung cancer (LC) has seriously affected human health and longevity. Chinese medicine is a complex system guided by traditional Chinese medicine theories (TCM). Nowadays, the clinical application of TCM for LC patients has become the focus for its effectiveness and security. In this paper, we will analyze and study the mechanism of Xia Qi Decoction (XQD) in the treatment of LC. The results collectively show that XQD could act on 41 therapeutic targets of LC. At the same time, 8 of 41 targets were significantly expressed in immune tissues and cells by activating CD8+T cells to promote apoptosis of cancer cells. It reveals the molecular mechanism of XQD in the treatment of LC from the perspective of network pharmacology. In addition, in the treatment of LC, XQD can activate (up-regulate) the function of immune cells, promote the apoptosis of tumor cells, and have an active anti-tumor immune effect. In conclusion, this study reveals the unique advantages of traditional Chinese medicine in the treatment of cancer, in reinforcing the healthy qi and eliminating the pathogenic factors. More research, however, is needed to verify the potential mechanisms.

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“…Beta-sitosterol, a phytosterol induces anticancer properties in different cancers based on different mechanisms [38]. It is indicated that beta-sitosterol induced G0/G1 cell cycle arrest in NSCLC cells possibly by inactivating the TGF-β/Smad2/3/c-Myc pathway [39]. Beta-Sitosterol which has been shown to have reverse MDR on leukemia via induces G2/M arrest, endoreduplication, and apoptosis through the Bcl-2 and PI3K/Akt signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

Song

Guo

Sun

et al. 2020

Preprint

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Background: Leukemia was listed by the World Health Organization as one of the five most intractable diseases in the world. The multi-drug resistance (MDR) of leukemia cells limits the efficacy of anti-tumor drugs and is the major reason for the chemotherapy failure and recurrence of leukemia chemotherapy. Some studies have shown that Euphorbiae semen (ES) possesses the characteristics of new therapeutic drugs for MDR. However, the molecular mechanisms and active compounds have not yet been fully clarified. Therefore, there is a need for explore its active compounds and demonstrate its mechanisms through network pharmacology and molecular docking technology.Method: First, the TCMSP database was searched and screened the active compounds of the ES, supplemented with compounds verified by literature, so as to further identify the core compounds in the active ingredient. Simultaneously, the TCMSP and Swiss database were searched to the targets of active compounds, and the targets of reverses leukemia multidrug resistance (RL-MDR) were screened in the relevant databases, such as GeneCards and DrugBank. Then, the targets of active compounds were intersected with RL-MDR targets to obtain potential targets of ES acting on MDR. The compound–target network was constructed by Cytoscape. The target protein–protein interaction network was built using STRING and Cytoscape database. Second, the R language and DAVID database were used to analyse Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment. Finally, molecular docking method was utilized to investigate the binding activity between the core targets and the active compounds of ES.Results: Compound–target network mainly contained 22 compounds and 81 corresponding targets. Finally, seven components in ES were selected and 10 core targets were identified; Key targets contained JUN, CASP3, MAOA, AR, PPARG, DRD2, ADRA2A, CHRM2, PTGS2 and MAPK14. GO enrichment analysis indicated the main biological functions of potential genes of ES in the treatment of MDR. KEGG pathway enrichment analysis showed the main pathways, mainly including apoptosis, pathways in cancer, p53 signaling pathway, VEGF signaling pathway, TNF signaling pathway and PI3K–Akt signaling pathway. Finally, we chose the top 10 common targets for molecular docking with the 7 active compounds of ES. The results of molecular docking indicated that the compounds of ES, which had good affinity with targets. Conclusion: The molecular mechanism of ES in the treatment of MDR showed the synergistic reaction of multi-compound, multi-target, and multi-pathway of traditional Chinese medicine, which provided ideas for further clinical research.

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BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

Cited by 33 publications

References 42 publications

Inhibition of Ep3 attenuates migration and promotes apoptosis of non‑small cell lung cancer cells via suppression of TGF‑β/Smad signaling

Inhibition of Ep3 attenuates migration and promotes apoptosis of non‑small cell lung cancer cells via suppression of TGF‑β/Smad signaling

Network Pharmacology Approach Reveals the Potential Immune Function Activation and Tumor Cell Apoptosis Promotion of Xia Qi Decoction in Lung Cancer

Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

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