Avaliação dos efeitos do inibidor multiquinase sorafenibe sobre as células musculares lisas arteriais de Rattus norvegicus: estudo in vitro / Evaluation of the effects of the multikinase inhibitor sorafenib on the arterial smooth muscle cells of Rattus norvegicus: an in vitro study
DOI:
https://doi.org/10.34117/bjdv7n12-361Keywords:
sorafenibe, reestenose arterial, inibidor multiquinase.Abstract
A ré estenose arterial é um processo inflamatório que pode ocorrer após colocação de stent por cateterismo. Os stents farmacológicos surgiram para reduzir esse problema e o inibidor multiquinase sorafenibe demonstrou ser um composto com ação efetiva. Este estudo in vitro avaliou os efeitos do sorafenibe sobre a citotoxicidade, migração celular e distribuição das células nas fases do ciclo celular. A linhagem celular de músculo liso de rato A7r5 foi tratada com sorafenibe em concentrações que variaram de 0 a 5 μM. Os efeitos citotóxicos foram avaliados por dois ensaios colorimétricos, MTT e SRB após 24 horas de tratamento. A distribuição das células nas fases do ciclo celular foi avaliada por citometria de fluxo e a capacidade de cicatrização/migração celular pelo ensaio scratch wound assay. Comparado com o controle positivo paclitaxel, o sorafenibe demonstrou um efeito 1,6 vezes maior na redução da proliferação celular. Na avaliação do ciclo celular, o sorafenibe mostrou um bloqueio na fase G0/G1. Além disso, o sorafenibe aumentou o número de A7r5 células na fase sub-G1, sugerindo morte celular. No entanto, no estudo de cicatrização/migração celular, não foi observado efeito quando comparado ao controle negativo. Assim, esses resultados in vitro sugerem que o sorafenibe é eficaz para uso em stents farmacológicos, sugerindo uma continuidade na investigação desse fármaco.
References
Azevedo, r.b., botelho, b.g., hollanda, j.v.g., ferreira, l.v.l., junqueira de andrade, l.z., oei, s.s.m.l., mello, t.s., muxfeldt, e.s., 2021. Covid-19 and the cardiovascular system: a comprehensive review. J. Hum. Hypertens. 35, 4-11. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7384729/
Broecker-preuss, m., müller, s., britten, m., worm, k., schmid, k.w., mann, k., fuhrer, d., 2015. Sorafenib inhibits intracellular signaling pathways and induces cell cycle arrest and cell death in thyroid carcinoma cells irrespective of histological origin or braf mutational status. Bmc cancer. 26, 184. Url: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1186-0
Buccheri, d., piraino, d., andolina, g., cortese, b., 2016. Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment. J. Thorac. Dis. 8, e1150-e1162. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5107494/
Egidio, a.n.; b.n.; junqueira, c.f.s.; martins, f.r.; fabri júnior, j.; rodrigues, j.f.; de siqueira, l.g.g.; de oliveira, l.r.b.; ferreira, m.b.s.; antunes, v.r.m., 2020. Implicações cardiovasculares na covid-19: uma revisão sistemática. Brazilian journal of development, v. 6, p. 82111-82128, 2020. Url: https://www.brazilianjournals.com/index.php/brjd/article/view/18888
Garten, a., grohmann, t., kluckova, k., lavery, g.g., kiess, w., penke, m., 2019. Sorafenib-induced apoptosis in hepatocellular carcinoma is reversed by sirt1. Int. J. Mol. Sci. 20, 4048. Url: https://www.mdpi.com/1422-0067/20/16/4048
Guo, q., lu, l., liao, y., wang, x., zhang, y., liu, y., huang, s., sun, h., li, z., zhao, l., 2018. Influence of c-src on hypoxic resistance to paclitaxel in human ovarian cancer cells and reversal of fv-429. Cell death dis. 8, e3178. Url: https://www.nature.com/articles/cddis2017367
He, s., wei, y.z., wang, g.l., xu, y.y., zhou, j.m., zhang, y.x., chen, l., 2013. Study of rna interference targeting net-1 combination with sorafenib for hepatocellular carcinoma therapy in vitro and in vivo. 2013. Gastroenterol. Res. Pract. 2013:685150.
Hernández, c., 2017. Stents medicados en cardiología intervencionista. Rev. Colombiana cardiol. 24, 31-38. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3838818/
Herrington, w., lacey, b., sherliker, p., armitage, j., lewington, s., 2016. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ. Res. 118, 535-546. Url: https://www.ahajournals.org/doi/10.1161/circresaha.115.307611?Url_ver=z39.88-
&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Huang, c., zhang, w., zhu, y., 2019. Drug-eluting stent specifically designed to target vascular smooth muscle cell phenotypic modulation attenuated restenosis through the yap pathway. Am. J. Physiol. Heart circ. Physiol. 317, h541-h551. Url: https://journals.physiology.org/doi/full/10.1152/ajpheart.00089.2019?Rfr_dat=cr_pub++0pubmed&url_ver=z39.88-2003&rfr_id=ori%3arid%3acrossref.org
International standard iso 10993-5-iso/en10993-5, 2009. Biological evaluation of medical devices, part 5: tests for cytotoxicity in vitro methods, third edition. Iso, geneva. Url: https://www.iso.org/standard/36406.html
Kacan, t., altun, a., altun, g.g., kacan, s.b., sarac, b., seker, m.m., bahceci, a., babacan, n., 2014. Investigation of antitumor effects of sorafenib and lapatinib alone and in combination on mcf-7 breast cancer cells. Asian pac. J. Cancer prev. 15, 3185-3159. Url: http://journal.waocp.org/?Sid=entrez:pubmed&id=pmid:24815468&key=2014.15.7.3185
Kalliokoski, t., kramer, c., vulpetti, a., gedeck, p., 2013. Comparability of mixed ic₅₀ data - a statistical analysis. Plos one. 8, e61007. Url: https://journals.plos.org/plosone/article?Id=10.1371/journal.pone.0061007
Kim, d.h., jeong, y.i., chung, c.w., kim, c.h., kwak, t.w., lee, h.m., kang, d.h., 2013. Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells. Int. J. Nanomedicine. 8, 1697-1711. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3646502/
Mosmann, t., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 65, 55-63. Url: https://www.sciencedirect.com/science/article/abs/pii/0022175983903034?Via%3dihub
Nicoletti, i., migliorati, g., pagliacci, m.c., grignani, f., riccardi, c., 1991. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immunol. Methods. 139, 271-279. Url: https://www.sciencedirect.com/science/article/abs/pii/002217599190198o?Via%3dihub
Omeh, d.j., shlofmitz, e., 2021. Restenosis. In: statpearls [internet]. Treasure island (fl): statpearls publishing. Url: https://www.ncbi.nlm.nih.gov/books/nbk545139/
Reckelhoff, c.r., lejeune, a., thompson, p.m., shiomitsu, k., 2019. In vitro effects of the chemotherapy agent water-soluble micellar paclitaxel (paccal vet) on canine hemangiosarcoma cell lines. Vet. Comp. Oncol. 17, 32-41. Url: https://onlinelibrary.wiley.com/doi/10.1111/vco.12442
Schult, c., dahlhaus, m., ruck, s., sawitzky, m., amoroso, f., lange, s., etro, d., glass, a., fuellen, g., boldt, s., wolkenhauer, o., neri, l.m., freund, m., junghanss, c., 2010. The multikinase inhibitor sorafenib displays significant antiproliferative effects and induces apoptosis via caspase 3, 7 and parp in b- and t-lymphoblastic cells. Bmc cancer. 10, 560. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2972283/?Report=reader
Silva, b.v., horta, b.a.c., alencastro, r.b., angelo, c., 2009. Kinase protein: structural features and chemical inhibitors. Quim. Nova. 32, 453-462. Url: https://www.scielo.br/j/qn/a/wl8tzqqxdhc3ycxb7w4gtnk/abstract/?Format=html&lang=en
Skehan, p., storeng, r., scudiero, d., monks, a., mcmahon, j., vistica, d., warren, j.t., bokesch, h., kenney, s., boyd, m.r., 1990. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer inst. 82, 1107-1112. Url: https://academic.oup.com/jnci/articleabstract/82/13/1107/970741?Redirectedfrom=fulltext
Timóteo, a.t., mota carmo, m., soares, c., cruz ferreira, r., 2019. Is metabolic syndrome a prognostic marker in patients at high cardiovascular risk? A long-term cohort study. Rev. Port. Cardiol. 38, 325-332. Url: https://www.sciencedirect.com/science/article/pii/s0870255118300696?Via%3dihub
Vockel, m., pollok, s., breitenbach, u., ridderbusch, i., kreienkamp, h.j., brandner, j.m., 2011. Somatostatin inhibits cell migration and reduces cell counts of human keratinocytes and delays epidermal wound healing in an ex vivo wound model. Plos one. 6, e19740. Url: https://journals.plos.org/plosone/article?Id=10.1371/journal.pone.0019740
Walter, m.n., wright, k.t., fuller, h.r., macneil, s., johnson, w.e., 2010. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Exp. Cell. Res. 316, 1271-1281. Url: https://www.karger.com/article/abstract/438545
Weaver, b.a., 2014. How taxol/paclitaxel kills cancer cells. Mol. Biol. Cell. 25, 2677-2681. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4161504/
Wei, j.c., meng, f.d., qu, k., wang, z.x., wu, q.f., zhang, l.q., pang, q., liu, c., 2015. Sorafenib inhibits proliferation and invasion of human hepatocellular carcinoma cells via up-regulation of p53 and suppressing foxm1. Acta pharmacol. Sin. 36, 241-251. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4326788/
Wilhelm, s.m., adnane, l., newell, p., villanueva, a., llovet, j.m., lynch, m., 2008. Preclinical overview of sorafenib, a multikinase inhibitor that targets both raf and vegf and pdgf receptor tyrosine kinase signaling. Mol. Cancer ther. 7, 3129-3140. Url: https://mct.aacrjournals.org/content/7/10/3129
World health organization 2021. Programes and projects: cardiovascular disease [online]. Disponível em: http://www.who.int/cardiovascular_diseases/en/.
Wu, q., wang, x., pham, k., luna, a., studzinski, g.p., liu, c., 2019. Enhancement of sorafenib-mediated death of hepatocellular carcinoma cells by carnosic acid and vitamin d2 analog combination. J. Steroid biochem. Mol. Biol. 5, 105524. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7015782/
Yu, c., friday, b.b., lai, j.p., yang, l., sarkaria, j., kay, n.e., carter, c.a., roberts, l.r., kaufmann, s.h., adjei, a.a., 2006. Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through akt and c-jun nh2-terminal kinase pathways. Mol. Cancer ther. 5, 2378-2387. Url: https://mct.aacrjournals.org/content/5/9/2378.long
Zhan, x.k., li, j.l., zhang, s., xing, p.y., xia, m.f., 2018. Betulinic acid exerts potent antitumor effects on paclitaxel-resistant human lung carcinoma cells (h460) via g2/m phase cell cycle arrest and induction of mitochondrial apoptosis. Oncol. Lett. 16, 3628-3634. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6