Bupivacaine inhibits angiogenesis through oxidative stress‐dependent inhibition of Akt/mTOR and activation of AMPK

Zhu, Guanhua; Xu, Wei; Dan, Jiapeng; Xia, Rui; Liu, Weiwei

doi:10.1111/fcp.12554

Cited by 10 publications

(10 citation statements)

References 30 publications

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“…In agreement with our findings, the LINC00470 expression was noticeably enhanced in gastric cancer tissues and cell lines, which was likewise associated with poor prognosis, distant metastasis, and tumor-node-metastasis stage (8). Additionally, LINC00470 plays a vital role in the tumorigenesis of glioblastoma and its high expression correlates with poor prognosis of patients with glioblastoma (18). Furthermore, LINC00470 can promote malignant behaviors of hepatocellular carcinoma cells (26), supporting the oncogenic effect of LINC00470 in cancers.…”

Section: Discussionsupporting

confidence: 90%

LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

Song

Zuo

et al. 2021

Front. Oncol.

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ObjectivesIncreasing researches emphasize the importance of long non-coding RNAs (lncRNAs) in the development of endometrial cancer (EC). There is wide recognition that LINC00470 is a critical participant in the tumorigenesis of cancers such as gastric cancer and glioblastoma, but its possible effects on EC progression remain to be explored.MethodsWe collected EC tissues and cells, where the expression of LINC00470 was determined, and followed by the Kaplan-Meier analysis of EC patient survival. We next examined the effect of LINC00470 and phosphatase and tensin homolog (PTEN) on EC cell migration, invasion, tube formation in vitro, and angiogenesis in mice xenografted with tumor after gain- or loss-of-function treatments. RNA pull-down, Co-IP, and ChIP experiments were performed to analyze the targeting relationships among LINC00470, MYC and DNMT3a.ResultsLINC00470 was aberrantly upregulated in EC and its high expression correlated to prognosis of EC patients. LINC00470 promoted invasiveness, migration, and angiogenesis of EC cells, and facilitated tumorigenesis and metastasis in vivo, but those effects were reversed by up-regulating PTEN. Functionally, LINC00470 bound to MYC in EC and that LINC00470 stimulated the binding of MYC to DNMT3a, and thus recruited DNMT3a through MYC to promote PTEN methylation.ConclusionsOur findings revealed that LINC00470 stimulated PTEN methylation to inhibit its expression by MYC-induced recruitment of DNMT3a, thus aggravating EC.

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Section: Discussionsupporting

confidence: 90%

LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

Song

Zuo

et al. 2021

Front. Oncol.

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“…[12] In endothelial cells, bupivacaine suppresses angiogenesis through oxidative stress-dependent inhibition of the Akt/mTOR pathway and activation of the AMPK pathway. [46] In our study, we found that bupivacaine reduced the protein levels of total and phosphorylated EGFR and ERBB3, thus impaired the activation of downstream PI3K/Akt and MAPK pathways in HCC cells. It is reported that local anesthetic Lidocaine inhibits the shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF), thus reduced EGFR phosphorylation and suppressed the invasion of human cancer cells.…”

Section: Discussionsupporting

confidence: 49%

Local anesthetic bupivacaine inhibits proliferation and metastasis of hepatocellular carcinoma cells via suppressing PI3K/Akt and MAPK signaling

Wang

Guo

Guan

et al. 2021

J Biochem & Molecular Tox

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide.Retrospective studies suggest that using local/regional anesthetic (LA/RA) is associated with better outcomes in primary HCC patients. In this study, we evaluated the effects of LA/RA bupivacaine in HCC cells and the underlying molecular mechanisms. The biological functions of bupivacaine in HCC cells were evaluated by transcriptome RNA sequencing, cell viability assay, bromodeoxyuridine incorporation assay, colony formation assay, flow cytometry, western blot, wound healing assay, transwell cell migration assay, tumor xenograft formation, and lung metastasis assay. Bupivacaine suppressed proliferation and induced apoptosis of HepG2 and SNU-449 cells in a time-and dose-dependent manner. Bupivacaine treatment also decreased colony formation, migration, and invasion of HepG2 and SNU-449 cells. In mouse models, bupivacaine repressed tumor xenograft growth and lung metastasis of HepG2 cells. Transcriptome sequencing of HepG2 cells suggested that PI3K/Akt and MAPK signaling pathways were suppressed by bupivacaine treatment. In western blot analysis, bupivacaine reduced the expression of total and phosphorylated Akt, mTOR, and MAPK. Furthermore, reactivated PI3K/Akt and MAPK signaling by EGF or NRG1 partially reversed the effects of bupivacaine on cell growth, colony formation, and invasion of HCC cells. Local anesthetic bupivacaine suppressed proliferation, migration and invasion, and induced apoptosis of HCC cells. Our results provided novel insights into the local anesthetic bupivacaine in the therapy of HCC patients.

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“…Zhai et al ( 53 ) have proved that overexpressed SIRT1 increases the phosphorylation levels of PI3K and AKT, thereby inhibiting the apoptosis of cardiomyocytes induced by high glucose and reducing its oxidative stress response. MTOR is an important downstream target of AKT and takes part in the expression and transcription of related proteins and genes, thus affecting biological activities such as inflammation, oxidative stress, apoptosis, and so on ( 54 , 55 ). The over-expressed SIRT1 activates PI3K through tyrosine kinase receptor, then the activated PI3K promotes the phosphorylation of AKT, activates MTOR, and inhibits oxidative stress and inflammation ( 56 ).…”

Section: Resultsmentioning

confidence: 99%

Antioxidant Activity and the Potential Mechanism of the Fruit From Ailanthus altissima Swingle

Cheng

Yang

et al. 2021

Front. Vet. Sci.

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The fruits of Ailanthus altissima Swingle (AS) possess a variety of pharmacological activities. Its antioxidant activity and the potential mode of action have not yet been investigated. In in vitro studies, AS revealed the strong reducing power and DPPH scavenging effect, but hydroxyl radical scavenging activity and ferrous ions-chelating ability were not strong. Meanwhile, the oxidative stress RAW264.7 cell injury model was established, the low and medium-doses of AS showed significant protective effects on the viability of H2O2-treated cells by CCK-8 method. Besides, three doses of AS all increased the activities of SOD, CAT, and GSH-Px and decreased the MDA level compared with the H2O2 group, suggesting it significantly relieved oxidative stress of cells. The active ingredients and related targets of AS were collected by HERB and Swiss Target Prediction database, the common targets of drugs and diseases database were conducted by GeneCards database platform and the Venny platform. We screened the core targets of AS like threonine kinase1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), sirtuin-1 (SIRT1), mechanistic target of rapamycin kinase (MTOR) by STRING database, and the key pathways involved PI3K-AKT and FoxO signaling pathway by KEGG pathway enrichment analysis. Besides, qRT-PCR revealed AS preconditioning significantly up-regulated the expression level of AKT1, SIRT1, MAPK1, and MTOR in model cells, and the effect was related to the regulation of FoxO and PI3K/AKT signaling pathway. In summary, AS showed significant antioxidant activity and its potential mechanism was regulating FoxO and PI3K/AKT signaling pathway.

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Bupivacaine inhibits angiogenesis through oxidative stress‐dependent inhibition of Akt/mTOR and activation of AMPK

Cited by 10 publications

References 30 publications

LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

Local anesthetic bupivacaine inhibits proliferation and metastasis of hepatocellular carcinoma cells via suppressing PI3K/Akt and MAPK signaling

Antioxidant Activity and the Potential Mechanism of the Fruit From Ailanthus altissima Swingle

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