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      Levobupivacaine inhibits proliferation and promotes apoptosis of breast cancer cells by suppressing the PI3K/Akt/mTOR signalling pathway

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          Abstract

          Objective

          This study aimed to test the hypothesis that levobupivacaine has anti-tumour effects on breast cancer cells.

          Results

          Colony formation and transwell assay were used to determine breast cancer cells proliferation. Flow Cytometry (annexin V and PI staining) was used to investigate breast cancer cells apoptosis. The effects of levobupivacaine on cellular signalling and molecular response were studied with Quantitative Polymerase Chain Reaction and western blot. Induction of apoptosis was confirmed by cell viability, morphological changes showed cell shrinkage, rounding, and detachments from plates. The results of the western blot and Quantitative Polymerase Chain Reaction indicated activation of active caspase-3 and inhibition of FOXO1. The results of the flow Cytometry confirmed that levobupivacaine inhibited breast cancer cell proliferation and enhanced apoptosis of breast cancer cells. Quantitative Polymerase Chain Reaction and Western blot analysis showed increased p21 and decreased cyclin D. Quantitative Polymerase Chain Reaction and western blot analysis showed that levobupivacaine significantly increased Bax expression, accompanied by a significant decreased Bcl-2 expression and inhibition of PI3K/Akt/mTOR signalling pathway. These findings suggested that levobupivacaine inhibits proliferation and promotes breast cancer cells apoptosis in vitro.

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          Most cited references36

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          CDK inhibitors: positive and negative regulators of G1-phase progression.

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            Cellular survival: a play in three Akts.

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              FOXOs, cancer and regulation of apoptosis.

              Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of physiological and pathological processes including cancer. The importance of FOXO factors ascribes them under multiple levels of regulation including phosphorylation, acetylation/deacetylation, ubiquitination and protein-protein interactions. As FOXO factors play a pivotal role in cell fate decision, mounting evidence suggests that FOXO factors function as tumor suppressors in a variety of cancers. FOXOs are actively involved in promoting apoptosis in a mitochondria-independent and -dependent manner by inducing the expression of death receptor ligands, including Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, and Bcl-2 family members, such as Bim, bNIP3 and Bcl-X(L), respectively. An understanding of FOXO proteins and their biology will provide new opportunities for developing more effective therapeutic approaches to treat cancer.
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                Author and article information

                Contributors
                akosuakotaa@hotmail.com
                sylvanuskampo@yahoo.com , skampo@uhas.edu.gh
                568059575@qq.com
                mnomanr8894@gmail.com
                gbepoo@gmail.com
                aglaisarredondo@yahoo.com
                jagudogo2@gmail.com
                evans.narh@gmail.com
                yanqiu63@126.com
                wqp.89@163.com
                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                1756-0500
                17 August 2020
                17 August 2020
                2020
                : 13
                : 386
                Affiliations
                [1 ]GRID grid.411971.b, ISNI 0000 0000 9558 1426, Department of Anaesthesiology, , Dalian Medical University, ; Dalian, China
                [2 ]GRID grid.452435.1, Department of Anaesthesiology, , First Affiliated Hospital of Dalian Medical University, ; Dalian, China
                [3 ]GRID grid.411971.b, ISNI 0000 0000 9558 1426, Department of Biochemistry and Molecular Biology, , Dalian Medical University, ; Dalian, China
                [4 ]GRID grid.449729.5, Department of Anaesthesia and Critical Care, School of Medicine, , University of Health and Allied Sciences, ; Ho, Ghana
                [5 ]GRID grid.442305.4, ISNI 0000 0004 0441 5393, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, , University for Development Studies, ; Tamale, Ghana
                [6 ]Departments of Anaesthesia and Critical Care, Ridge Hospital, Accra, Ghana
                [7 ]Department of Medicine, Princefied University, Ho, Ghana
                Article
                5191
                10.1186/s13104-020-05191-2
                7430121
                32807213
                b62d0487-a199-4739-adb0-f7d715155406
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 9 June 2020
                : 16 July 2020
                Funding
                Funded by: Liaoning Natural Science Foundation
                Award ID: 20170540290
                Award Recipient :
                Funded by: Key Laboratory of Liaoning Provincial Education Department
                Award ID: LZ2016002
                Award Recipient :
                Categories
                Research Note
                Custom metadata
                © The Author(s) 2020

                Medicine
                levobupivacaine,proliferation,invasion,apoptosis,breast cancer
                Medicine
                levobupivacaine, proliferation, invasion, apoptosis, breast cancer

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