Elucidating the mechanisms of action of parecoxib in the MG-63 osteosarcoma cell line

Lemos, Sílvia; Sampaio‐Marques, Belém; Ludovico, Paula; Gaivão, Isabel; Palmeira, Carlos; Martins, Gabriela; Peixoto, Francisco; Pinto‐Leite, Rosário; Oliveira, Paula A.

doi:10.1097/cad.0000000000000901

Cited by 8 publications

(5 citation statements)

References 44 publications

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“…It has been reported that parecoxib could improve the postoperative analgesic effect and immune function when used for multimodal analgesia, and further postpone postoperative cancer recurrence [ 12 , 13 ]. Other studies have reported that parecoxib shows antitumor effects against human osteosarcoma, glioblastoma, and intestinal cancers [ 14 – 16 ]. Studies have further revealed the important role of parecoxib in the inhibition of vascular formation in cancer.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE:Parecoxib inhibits esophageal squamous cell carcinoma progression via the PDK1–AKT pathway

Huang

et al. 2022

Cell Mol Biol Lett

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Background Parecoxib plays an important role in inhibition of human cancer. However, the effect of parecoxib on esophageal squamous cell carcinoma (ESCC) is still not well known. The purpose of this study was to investigate the effect of parecoxib on ESCC and its underlying mechanism. Methods RNA-sequence analysis was performed to identify functional alterations and mechanisms. Cell cycle, proliferation, invasion, and migration were assessed using flow cytometry, CCK-8 assay, colony formation, transwell, and wound healing assays. Extracellular matrix (ECM) degradation was detected by substrate gel zymography and 3D cell culture assay. Western blotting was used to detect parecoxib-dependent mechanisms involving cell cycle, proliferation, invasion, and migration. Tumor formation in vivo was detected by mouse assay. Results Functional experiments indicated that parecoxib induced ESCC cell cycle arrest in G2 phase, and inhibited cell proliferation, invasion, and migration in vitro. Western blotting revealed that parecoxib downregulated the phosphorylation levels of AKT and PDK1, as well as the expression of the mutant p53, cyclin B1, and CDK1, while upregulating p21waf1. Parecoxib inhibited matrix metalloproteinase-2 (MMP2) secretion and invadopodia formation, which were related to ECM degradation. Furthermore, we found that parecoxib suppressed ESCC growth in heterotopic tumor models. Conclusion Parecoxib inhibits ESCC progression, including cell cycle, proliferation, invasion, and migration, via the PDK1–AKT signaling pathway.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE:Parecoxib inhibits esophageal squamous cell carcinoma progression via the PDK1–AKT pathway

Huang

et al. 2022

Cell Mol Biol Lett

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“…A case report describes an osteosarcoma patient receiving the cyclooxygenase 2 (COX2) inhibitors celelecoxib and thalidomide one month after treatment with lung metastases. It has also been found that celecoxib and thalidomide inhibit proliferation of osteosarcoma cells in a dose-dependent manner 29 . These studies support anti-inflammatory agents as potential therapeutic strategies for osteosarcoma patients.…”

Section: Discussionmentioning

confidence: 99%

Ebastine exerts antitumor activity and induces autophagy by activating AMPK/ULK1 signaling in an IPMK-dependent manner in osteosarcoma

Zhang¹,

Li²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.

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“…CD3 represents all T lymphocytes, which can also be divided into CD4+ T cells and CD8+ T cells. Among them, CD4+T cells mediate the functions of helper T cells (T), NKT cells, macrophages, and dendritic cells, while CD8+ lymphocytes mediate the functional changes of cytotoxic T lymphocytes (CTL) [12,13]. Te PBLS detection can evaluate the changes of lymphocyte subsets and the steady-state changes of lymphocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between PBLS and Osteosarcoma Distribution in Different Subgroups and the Survival and Prognosis of Osteosarcoma

Luo

Zhou

2023

Journal of Oncology

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Objective. To analyze the differences in the distribution of lymphocytes (PBLS) in different subgroups of osteosarcoma (OS) and the predictive value of related parameters on the survival prognosis of OS. Methods. For retrospective analysis, 80 patients with malignant OS diagnosed and treated in our hospital from June 2016 to June 2017 were selected as the observation group, and 80 patients with benign bone tumors during the same period were selected as the control group. Patients in the observation group were followed up for three years and grouped according to the tumor diameter, stage, metastasis, and prognosis. Fasting venous blood was collected from each group and the levels of CD3+, CD3+CD4+, and CD3+CD8+ were detected. Meanwhile, the ratio of CD4+/CD8+, CD4+/CD3+, and CD8+/CD3+ was calculated and compared. Kaplan–Meier survival curve was used to analyze the relationship between PBLS parameters and OS survival. The area under the curve (AUC), sensitivity, and specificity of each entry index were analyzed by the receiver operating characteristic curve (ROC curve). Results. The CD3+CD8+ level and CD4+/CD3+ ratio in the observation group were significantly higher than those in the control group ( P < 0.05 ). The level of CD3+CD8+ in the patients with tumor diameter ≥ 11 cm was observably higher than that in the patients with tumor diameter <11 cm ( P < 0.05 ). The levels of CD3+CD4+ and the ratio of CD4+/CD8 and CD4+/CD3+ of patients in stage III were markedly lower than those of patients in stage II, while the ratio of CD8+/CD3+ and the levels of CD3+CD8+ were prominently higher than those of patients in stage II ( P < 0.05 ). The CD3+CD4+ level and CD4+/CD3+ ratio of patients in the metastatic group before treatment, the metastatic group after treatment, and the nonmetastatic group after treatment increased successively, while the ratio of CD4+/CD8+ and CD8+/CD3+ and the level of CD3+CD8+ decreased successively ( P < 0.05 ). The CD3+CD4+ level and CD4+/CD3+ ratio in the poor prognosis group were significantly higher than those in the good prognosis group, whereas the ratio of CD8+/CD3+ and CD4+/CD8+ and the level of CD3+CD8+ were significantly lower than those in the poor prognosis group ( P < 0.05 ). ROC curve analysis showed that the AUC of CD4+/CD8+ and CD4+/CD3+ in predicting poor prognosis in patients with OS was notably higher than other indicators, which were 0.818 and 0.866, respectively ( P < 0.05 ). Kaplan–Meier survival curve results revealed that patients with CD3+CD4+ ≤ 5.15, CD3+CD8+ > 3.85, CD4+/CD8+ ≤ 1.42, CD4+/CD3+ ≤ 0.50, and CD8+/CD3+ > 0.38 had longer survival. Conclusion. The distribution of PBLS parameters varied widely among different subgroups of OS. Patients with poor prognosis had a higher ratio of CD4+/CD8+ and CD4+/CD3+, which were related to the survival of patients with OS. Moreover, both the ratio of CD4+/CD8+ and CD4+/CD3+ had certain predictive values in terms of survival and prognosis of OS. Therefore, regular clinical monitoring of patients’ immune function could help predict disease changes and assess prognosis.

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Elucidating the mechanisms of action of parecoxib in the MG-63 osteosarcoma cell line

Cited by 8 publications

References 44 publications

RETRACTED ARTICLE:Parecoxib inhibits esophageal squamous cell carcinoma progression via the PDK1–AKT pathway

RETRACTED ARTICLE:Parecoxib inhibits esophageal squamous cell carcinoma progression via the PDK1–AKT pathway

Ebastine exerts antitumor activity and induces autophagy by activating AMPK/ULK1 signaling in an IPMK-dependent manner in osteosarcoma

The Relationship between PBLS and Osteosarcoma Distribution in Different Subgroups and the Survival and Prognosis of Osteosarcoma

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