Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins

Chiou, Shiun-Kwei; Hoa, Neil; Hodges, Amy; Ge, Lishen; Jadus, Martin R.

doi:10.1007/s10495-014-1002-3

Cited by 18 publications

(11 citation statements)

References 33 publications

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“…This observation may be due to the alteration of the inflammatory response to surgery [ 37 - 39 ]. Also, studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) have a preventative effect against the development and progression of GC [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer

et al. 2015

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BackgroundThe prognostic role of inflammation indices, such as the neutrophil-to-lymphocyte ratio (NLR) in gastric cancer (GC) remains controversial. We conducted a meta-analysis to determine the predictable value of NLR in the clinical outcome of GC patients.MethodsWe searched Embase, PubMed and the Cochrane Library database for relevant randomised controlled trials. Statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals of overall survival (OS) and progression-free survival (PFS) using either random-effect or fixed-effect models according to the heterogeneity of the included studies. An analysis was carried out based on data from nine studies to evaluate the association between NLR and OS in patients with GC.ResultsOur analysis indicated that elevated pre-treatment NLR predicted poorer OS (HR: 2.16, 95% CI: 1.86 to 2.51, P < 0.001) and PFS (HR 2.78, 95% CI: 1.95 to 3.96; P < 0.00001) in patients with GC. Over a 3-year follow-up period, high NLR was a significant predictor of poor outcomes at year 1 (HR 1.99; 95% CI: 1.39 to 2.85; P = 0.0002), year 2 (HR 2.24; 95% CI: 1.69 to 2.97; P < 0.00001) and year 3 (HR 2.80; 95% CI: 1.98 to 3.96; P < 0.00001).ConclusionsElevated preoperative NLR is associated with poorer rates of survival in GC patients and may play a role in GC surveillance programmes as a means of delivering more personalised cancer care.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-015-0530-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer

et al. 2015

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“…[15] Numerous studies have suggested that aspirin and/or other NSAIDs can be effective in the prevention and/or treatment of malignancies, such as cancers of the colon, [16] breast, [17,18] lung, [19] pancreas, [20] prostate, [21,22] ovarium, [23] squamous cell carcinoma and melanoma, [24] etc. Different NSAIDs have been reported to inhibit the growth and survival of cell lines established from a wide variety of cancers, including gastric cancer, [25,26] cancers of the colon, [27] lung, [28] urinary bladder, [29] osteosarcoma, [30] etc.…”

Section: Introductionmentioning

confidence: 99%

3d metal complexes with meloxicam as therapeutic agents in the fight against human glioblastoma multiforme and cervical carcinoma

Dyakova

Culiță

Zhivkova

et al. 2015

Biotechnology & Biotechnological Equipment

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The aim of our study was to evaluate the influence of selective non-steroidal anti-inflammatory drug meloxicam and its metal (Cu(II), Zn(II), Co(II), Ni(II)) complexes on the viability and proliferation of cultured humancarcinoma of the uterine cervix (HeLa) and glioblastoma multiforme (8MGBA) cells. The investigations were performed by short-term (24 hÀ96 h, with monolayer cultures) and long-term (16 d, with three-dimensional colonies of cancer cells) experiments by using methods with different molecular/cellular targets and mechanisms of action, such as thiazolyl blue tetrazolium bromide (MTT) test, neutral red uptake cytotoxicity assay, crystal violet staining, double staining with acridine orange and propidium iodide, alkaline version of single cell gel electrophoresis (comet assay) and colony-forming technique. The obtained results revealed that the application of the examined compounds at concentrations ranging from 5 mg/mL to 500 mg/mL induced cytopathological changes, including DNA damages in the treated cells and a significant decrease of their viability and proliferation in a time-and concentration-dependent manner. Metal complexes were found to have a more pronounced cytotoxic/cytostatic effect, when compared to their ligand meloxicam.

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“…Aurora-B, a serine/threonine kinase, plays a vital role in a variety of biological behaviors in cells, such as mitosis and the cell cycle (28). Recent evidence has demonstrated that Aurora-B accelerates the progression of lung cancer (12), gastric cancer (29), prostate cancer (30), and OS (27). Previously, we found that Aurora-B positive expression rate is increased in human OS tissues with pulmonary metastasis compared with that in non-metastasis tissues (31).…”

Section: Discussionmentioning

confidence: 99%

Aurora-B Knockdown Inhibits Osteosarcoma Metastasis by Inducing Autophagy via the mTOR/ULK1 Pathway

Liu

Song

et al. 2020

Preprint

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Background Autophagy plays an essential role in metastasis of malignancies. Although our studies showed that Aurora-B facilitate pulmonary metastasis in OS, the mechanism of Aurora-B kinase on autophagy and metastasis in OS has not been explored. Methods Clinical-pathological parameters and follow-up information was collected in OS patients. Immunohistochemical staining was performed to detect Aurora-B and LC3 protein in OS tissues. Short hairpin RNA transfection was used to silence Aurora-B in OS cells. Real-time quantitative PCR (RT-qPCR) was performed to detect Aurora-B mRNA expression in OS cells. Aurora-B and autophagy related protein were measured by Western blot. Transmission electron microscopy and laser scanning confocal microscopy were performed to observe the formation of autophagosomes and autolysosomes. Migratory and invasive ability of OS cells were measured by Wound healing and transwell assays. Orthotopic xenograft model was used to evaluate the effect of autophagy mediated by Aurora-B inhibition on pulmonary metastasis of OS. Results The elevated expression of Aurora-B protein in OS tissues negatively associated with the overall survival of OS patients. Further investigation has found that Aurora-B expression was negatively correlative with autophagy related protein LC3 in OS patient tissues. Knockdown Aurora-B stimulates autophagy and inhibits migratory and invasive ability of OS cells. Mechanistically, Aurora-B knockdown suppressed the mTOR/ULK1 signaling pathway and reactivation of the mTOR/ULK1 pathway decreased autophagy level. Furthermore, the inhibition effect of silencing Aurora-B on migration and invasion of OS was reversed by chloroquine and mTOR activator in vitro and vivo. Conclusions Our results suggest that silencing of Aurora-B stimulate autophagy via decreasing mTOR/ULK1 and result in inhibiting OS metastasis. Targeted Aurora-B/mTOR/ULK1 pathway may be a promising treatment strategy for OS patients.

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Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins

Cited by 18 publications

References 33 publications

Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer

Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer

3d metal complexes with meloxicam as therapeutic agents in the fight against human glioblastoma multiforme and cervical carcinoma

Aurora-B Knockdown Inhibits Osteosarcoma Metastasis by Inducing Autophagy via the mTOR/ULK1 Pathway

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