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  • br Statistical analysis br Data are presented


    4.11. Statistical analysis
    Data are presented as mean ± standard deviation. SPSS 16.0 (SPSS, Chicago, IL) software was applied to perform statistical analysis.
    Competing interests
    The authors declare that they have no competing interests.
    This research was supported by grants from Sichuan Provincial Department of Science and Technology key research and development projects (No. 2018ZX09201018-029), National Natural Science Foundation of China youth science foundation project (No. 81703820).
    Author contributions
    Conceived and designed the experiments: J.N. Zhao. Performed the
    experiments: A.Q. Zeng. Analyzed the data: H. Hua, L. Liu. Wrote the
    Appendix A. Supplementary data
    cells induced by microencapsulated betulinic Galactose1phosphate from sour jujube fruits through the mitochondria transduction pathway. Food Chem. 2013;138:1998–2007. 7. Liu CM, Qi XL, Yang YF, Zhang XD. Betulinic acid inhibits cell proliferation and fibronectin accumulation in rat glomerular mesangial cells cultured under high glucose condition. Biomed Pharmacother. 2016;80:338–342. 8. Fulda S, Kroemer G. Targeting mitochondrial apoptosis by betulinic acid in human cancers. Drug Discovery Today. 2009;14:885–890. 9. Luo R, Fang D, Chu P, Wu H, Zhang Z, Tang Z. Multiple molecular targets in breast cancer therapy by betulinic acid. Biomed Pharmacother. 2016;84:1321–1330. 10. Gheorgheosu D, Duicu O, Dehelean C, Soica C, Muntean D. Betulinic acid as a potent and complex antitumor phytochemical: a minireview. Anti-Cancer Agents Med Chem. 2014;14:936–945. 11. Hsu RJ, Hsu YC, Chen SP, et al. The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells. BMC Complement Altern Med. 2015;15:65. 12. Hsu TI, Chen YJ, Hung CY, et al. A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy. Oncotarget. 2015;6:13671–13687. 13. Chintharlapalli S, Papineni S, Lei P, Pathi S, Safe S. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors. BMC Cancer. 2011;11:371. 14. Hsu TI, Wang MC, Chen SY, et al. Betulinic acid decreases specificity protein 1 (Sp1) level via increasing the sumoylation of sp1 to inhibit lung cancer growth. Mol Pharmacol. 2012;82:1115–1128. 15. Li L, Du Y, Kong X, et al. Lamin B1 is a novel therapeutic target of betulinic acid in pancreatic cancer. Clin Cancer Res. 2013;19:4651–4661. 16. Reiner T, Parrondo R, de Las Pozas A, Palenzuela D, Perez-Stable C. Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity. PLoS One. 2013;8:e56234.
    17. Chintharlapalli S, Papineni S, Ramaiah SK, Safe S. Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors. Cancer Res. 2007;67:2816–2823. 18. Chowdhury I, Tharakan B, Bhat GK. Current concepts in apoptosis: the physiological suicide program revisited. Cell Mol Biol Lett. 2006;11:506–525. 19. Ricci JE, Munoz-Pinedo C, Fitzgerald P, et al. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell. 2004;117:773–786. 20. Marinho-Filho JD, Bezerra DP, Araujo AJ, et al. Oxidative stress induction by
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    Cellular Signalling
    journal homepage:
    Bevacizumab induces inflammation in MDA-MB-231 breast cancer cell line T and in a mouse model
    Layal EL-Hajjara,1, Nour Jalaleddinea,1, Abdullah Shaitob, Kazem Zibarac, Jalal M. Kazand,2, Jamal El-Saghird, Marwan El-Sabband,
    a Department of Biological and Environmental Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon
    b Department of Biological and Chemical Sciences, Faculty of Arts and Sciences, Lebanese International University, Beirut, Lebanon
    c ER045– Laboratory of Stem Cells, PRASE, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon
    d Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
    Keywords: Inflammation
    Angiogenesis NF-κB
    Connexin 43
    Breast cancer
    Background: Bevacizumab or Avastin® (Av) is an anti-vascular endothelial growth factor agent. It does not im-prove survival of breast cancer patients due to development of refractoriness. Av treatment was shown to in-crease inflammation in a diabetic mouse model, and also to induce epithelial-to-mesenchymal transition of non-transformed breast epithelia. This study aimed to understand if the Av-induced inflammatory microenvironment could be a mechanism of Av refractoriness. Expression profiles of inflammatory mediators, in vitro in MDA-MB-231 cells, in vivo in a mouse model xenografted with MDA-MB-231 cells and from archived cases of human breast carcinoma tissues were evaluated. Gap junctions are also crucial for angiogenesis and tumor cell extravasation. The effect of connexin 43 (Cx43) overexpression on the expression of inflammatory markers in MDA-MB-231 cells treated with Av was assessed.