Paclitaxel Modula a Proliferação e a Diferenciação de Células THP-1 Expostas ao Vírus SARS-CoV-2 Inativado

Autores

DOI:

https://doi.org/10.32635/2176-9745.RBC.2025v71n2.5107

Palavras-chave:

Neoplasias da Mama/tratamento farmacológico , Paclitaxel, COVID-19, Síndrome da Liberação de Citocina, Citotoxicidade Imunológica/efeitos dos fármacos

Resumo

Introdução: Pacientes oncológicos foram considerados grupo de risco para a covid-19. Estudos indicam que determinados tipos de câncer, como o de mama, podem apresentar respostas imunológicas diferenciadas. Evidências sugerem que o paclitaxel (PTX), quimioterápico amplamente utilizado no tratamento do câncer de mama, tem propriedade imunomoduladora, o que poderia contribuir para atenuar a resposta inflamatória causada pelo vírus SARS-CoV-2. Objetivo: Avaliar o efeito do PTX na linhagem de células imunes THP-1 ativadas pelo imunógeno não viral éster de forbol 12-O-tetradecanoilforbol13-acetato (TPA) e pelo vírus SARS-CoV-2 inativado oriundo da vacina CoronaVac (CVac). Método: Foi conduzido um estudo in vitro constituído, primeiramente, pela determinação da concentração mínima de CVac capaz de ativar as células THP-1. A seguir, foi investigada a ação citotóxica do PTX nas células THP-1, seguida da análise do seu efeito imunomodulador por meio da análise da taxa de proliferação celular, diferenciação citomorfológica, níveis de óxido nítrico, ânion superóxido e expressão gênica das citocinas fator de necrose tumoral alfa e interleucina 10. Resultados: Em 24 horas, a CVac 5% ativou as células THP-1, desencadeando proliferação e diferenciação celular mais significativas que o controle. Nenhum efeito citotóxico de PTX foi observado. O PTX diminuiu a taxa de diferenciação celular e os níveis de superóxido quando exposto concomitantemente com TPA ou CVac, mas não modulou a expressão gênica das citocinas. Conclusão: Os dados indicam que o PTX poderia modular a ativação imunológica in vitro frente a imunógenos virais e não virais, sugerindo que ele poderia atenuar a resposta inflamatória a antígenos, incluindo o SARS-CoV-2.

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Biografia do Autor

Everaldo Hertz, Universidade Federal de Santa Maria (UFSM). Santa Maria (RS), Brasil

Universidade Federal de Santa Maria (UFSM). Santa Maria (RS), Brasil

Referências

Chai C, Feng X, Lu M, et al. One-year mortality and consequences of COVID‐19 in cancer patients: a cohort study. IUBMB Life. 2021;73(10):1244-56. doi: https://doi.org/10.1002/iub.2536 DOI: https://doi.org/10.1002/iub.2536

Alagoz O, Lowry KP, Kurian AW, et al. Impact of the COVID-19 pandemic on breast cancer mortality in the US: estimates from collaborative simulation modeling. JNCI J Natl Cancer Inst. 2021;113(11):1484-94. doi: https://doi.org/10.1093/jnci/djab097 DOI: https://doi.org/10.1093/jnci/djab097

Pinato DJ, Tabernero J, Bower M, et al. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study. Lancet Oncol. 2021;22(12):1669-80. doi: https://doi.org/10.1016/S1470-2045(21)00573-8 DOI: https://doi.org/10.1016/S1470-2045(21)00573-8

Hertz E, Cruz IBM, Gonçalves CFA, et al. Does breast cancer have a lower risk of mortality from severe acute respiratory syndrome compared to other types of cancer? Evidence from Brazil, a heterogeneous population. Contrib LAS Cienc Soc. 2023;16(12):32178-97. doi: https://doi.org/10.55905/revconv.16n.12-186 DOI: https://doi.org/10.55905/revconv.16n.12-186

Abu Samaan TM, Samec M, Liskova A, et al. Paclitaxel’s mechanistic and clinical effects on breast cancer. Biomolecules. 2019;9(12):789. doi: https://doi.org/10.3390/biom9120789 DOI: https://doi.org/10.3390/biom9120789

Adhami M, Sadeghi B, Rezapour A, et al. Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis. BMC Biotechnol. 2021;21(1):22. doi: https://doi.org/10.1186/s12896-021-00680-z DOI: https://doi.org/10.1186/s12896-021-00680-z

Dan VM, Raveendran RS, Baby S. Resistance to intervention: paclitaxel in breast cancer. Mini-Rev Med Chem. 2021;21(10):1237-68. doi: https://doi.org/10.2174/1389557520999201214234421 DOI: https://doi.org/10.2174/1389557520999201214234421

Debien V, Marta GN, Agostinetto E, et al. Real-world clinical outcomes of patients with stage I HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab. Crit Rev Oncol Hematol. 2023;190:104089. doi: https://doi.org/10.1016/j.critrevonc.2023.104089 DOI: https://doi.org/10.1016/j.critrevonc.2023.104089

Zhu L, Chen L. Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett. 2019;24(1):40. doi: https://doi.org/10.1186/s11658-019-0164-y DOI: https://doi.org/10.1186/s11658-019-0164-y

Zanza C, Romenskaya T, Manetti AC, et al. Cytokine storm in COVID-19: Immunopathogenesis and therapy. Medicina (Mex). 2022;58(2):144. doi: https://doi.org/10.3390/medicina58020144 DOI: https://doi.org/10.3390/medicina58020144

Mohd Yasin ZN, Mohd Idrus FN, Hoe CH, et al. Macrophage polarization in THP-1 cell line and primary monocytes: a systematic review. Differentiation. 2022;128:67-82. doi: https://doi.org/10.1016/j.diff.2022.10.001

Dallavalasa S, Beeraka NM, Basavaraju CG, et al. The role of tumor associated macrophages (TAMs) in cancer progression, chemoresistance, angiogenesis and metastasis - Current status. Curr Med Chem. 2021;28(39):8203-36. doi: https://doi.org/10.2174/0929867328666210720143721 DOI: https://doi.org/10.2174/1875533XMTE20ODIe4

Jin L, Li Z, Zhang X, et al. CoronaVac: a review of efficacy, safety, and immunogenicity of the inactivated vaccine against SARS-CoV-2. Hum Vaccines Immunother. 2022;18(6):2096970. doi: https://doi.org/10.1080/21645515.2022.2096970 DOI: https://doi.org/10.1080/21645515.2022.2096970

Lund ME, To J, O’Brien BA, et al. The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus. J Immunol Methods. 2016;430:64-70. doi: https://doi.org/10.1016/j.jim.2016.01.012 DOI: https://doi.org/10.1016/j.jim.2016.01.012

Geraghty RJ, Capes-Davis A, Davis JM, et al. Guidelines for the use of cell lines in biomedical research. Br J Cancer. 2014;111(6):1021-46. doi: https://doi.org/10.1038/bjc.2014.166 DOI: https://doi.org/10.1038/bjc.2014.166

Conselho Nacional de Saúde (BR). Resolução n° 466, de 12 de dezembro de 2012. Aprova as diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Diário Oficial da União, Brasília, DF. 2013 jun 13; Seção I:59.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. doi: https://doi.org/10.1016/0022-1759(83)90303-4 DOI: https://doi.org/10.1016/0022-1759(83)90303-4

Barbisan F, Motta JDR, Trott A, et al. Methotrexate-related response on human peripheral blood mononuclear cells may be modulated by the Ala16Val-SOD2 gene polymorphism. PLoS ONE. 2014;9(10):e107299. doi: https://doi.org/10.1371/journal.pone.0107299 DOI: https://doi.org/10.1371/journal.pone.0107299

Organização para Cooperação e Desenvolvimento Econômico. Guidance document on good in vitro method practices. Paris: OECD; 2018. (OECD Series on testing and assessment)

Ates G, Vanhaecke T, Rogiers V, et al. Assaying cellular viability using the neutral red uptake assay. Methods Mol Biol. 2017;1601:19-26. doi: https://doi.org/10.1007/978-1-4939-6960-9_2 DOI: https://doi.org/10.1007/978-1-4939-6960-9_2

Repetto G, Del Peso A, Zurita JL. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc. 2008;3(7):1125-31. doi: https://doi.org/10.1038/nprot.2008.75 DOI: https://doi.org/10.1038/nprot.2008.75

Baxter EW, Graham AE, Re NA, et al. Standardized protocols for differentiation of THP-1 cells to macrophages with distinct M(IFNγ+LPS), M(IL-4) and M(IL-10) phenotypes. J Immunol Methods. 2020;478:112721. doi: https://doi.org/10.1016/j.jim.2019.112721 DOI: https://doi.org/10.1016/j.jim.2019.112721

Rasband WS. ImageJ software [Internet]. version 1.41. Bethesda: U.S. National Institutes of Health; 2009. [Acesso 2025 jan 25]. Disponivel em: https://imagej.net/ij/index.html

Weigert A, Von Knethen A, Fuhrmann D, et al. Redox-signals and macrophage biology. Mol Aspects Med. 2018;63:70-87. doi: https://doi.org/10.1016/j.mam.2018.01.003 DOI: https://doi.org/10.1016/j.mam.2018.01.003

Chang YY, Lu CW, Jean WH, et al. Phorbol myristate acetate induces differentiation of THP-1 cells in a nitric oxide-dependent manner. Nitric Oxide. 2021;109-110:33-41. doi: https://doi.org/10.1016/j.niox.2021.02.002 DOI: https://doi.org/10.1016/j.niox.2021.02.002

Tatsch E, Bochi GV, Pereira RDS, et al. A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem. 2011;44(4):348-50. doi: https://doi.org/10.1016/j.clinbiochem.2010.12.011 DOI: https://doi.org/10.1016/j.clinbiochem.2010.12.011

Morabito C, Rovetta F, Bizzarri M, et al. Modulation of redox status and calcium handling by extremely low frequency electromagnetic fields in C2C12 muscle cells: a real-time, single-cell approach. Free Radic Biol Med. 2010;48(4):579-89. https://doi.org/10.1016/j.freeradbiomed.2009.12.005 DOI: https://doi.org/10.1016/j.freeradbiomed.2009.12.005

Son SS, Kang JS, Lee EY. Paclitaxel ameliorates palmitate-induced injury in mouse podocytes. Med Sci Monit Basic Res. 2020;26. doi: https://doi.org/10.12659/MSMBR.928265 DOI: https://doi.org/10.12659/MSMBR.928265

Graph Pad: Prism [Internet]. Versão 9.4. Boston: GraphPad; 2020. [acesso 2024 dez 19]. Disponível em: https://www.graphpad.com/updates/prism-900-release-notes

Chanput W, Mes JJ, Wichers HJ. THP-1 cell line: an in vitro cell model for immune modulation approach. Int Immunopharmacol. 2014;23(1):37-45. doi: https://doi.org/10.1016/j.intimp.2014.08.002 DOI: https://doi.org/10.1016/j.intimp.2014.08.002

Barhoumi T, Alghanem B, Shaibah H, et al. SARS-CoV-2 coronavirus spike protein-induced apoptosis, inflammatory, and oxidative stress responses in THP-1-like-macrophages: potential role of angiotensin-converting enzyme inhibitor (perindopril). Front Immunol. 2021;12:728896. doi: https://doi.org/10.3389/fimmu.2021.728896 DOI: https://doi.org/10.3389/fimmu.2021.728896

Albrahim T, Alnasser MM, Al-Anazi MR, et al. In vitro studies on the immunomodulatory effects of pulicaria crispa extract on human THP-1 monocytes. Oxid Med Cell Longev. 2020;2020:7574606. doi: https://doi.org/10.1155/2020/7574606 DOI: https://doi.org/10.1155/2020/7574606

Yasin ZNM, Idrus FNM, Hoe CH, et al. Macrophage polarization in THP-1 cell line and primary monocytes: a systematic review. Differentiation. 2022;128:67-82. doi: https://doi.org/10.1016/j.diff.2022.10.001 DOI: https://doi.org/10.1016/j.diff.2022.10.001

Pan P, Shen M, Yu Z, et al. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun. 2021;12(1):4664. doi: https://doi.org/10.1038/s41467-021-25015-6 DOI: https://doi.org/10.1038/s41467-021-25015-6

Khatua S, Simal-Gandara J, Acharya K. Understanding immune-modulatory efficacy in vitro. Chem Biol Interact. 2022;352:109776. doi: https://doi.org/10.1016/j.cbi.2021.109776 DOI: https://doi.org/10.1016/j.cbi.2021.109776

Huang H, Li X, Zha D, et al. SARS-CoV-2 e protein-induced THP-1 pyroptosis is reversed by Ruscogenin. Biochem Cell Biol. 2023;101(4):303-12. doi: https://doi.org/10.1139/bcb-2022-0359 DOI: https://doi.org/10.1139/bcb-2022-0359

Liu T, Huang T, Li J, et al. Optimization of differentiation and transcriptomic profile of THP-1 cells into macrophage by PMA. PLoS One. 2023;18(7):e0286056. doi: https://doi.org/10.1371/journal.pone.0286056 DOI: https://doi.org/10.1371/journal.pone.0286056

Asnaashari S, Amjad E, Sokouti B. Synergistic effects of flavonoids and paclitaxel in cancer treatment: a systematic review. Cancer Cell Int. 2023;23(1):211. doi: https://doi.org/10.1186/s12935-023-03052-z DOI: https://doi.org/10.1186/s12935-023-03052-z

Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018;233(9):6425-40. doi: https://doi.org/10.1002/jcp.26429 DOI: https://doi.org/10.1002/jcp.26429

Wanderley CW, Colón DF, Luiz JPM, et al. Paclitaxel reduces tumor growth by reprogramming tumor-associated macrophages to an M1 profile in a TLR4-dependent manner. Cancer Res. 2018;78(20):5891-900. doi: https://doi.org/10.1158/0008-5472.CAN-17-3480 DOI: https://doi.org/10.1158/0008-5472.CAN-17-3480

Publicado

2025-05-15

Como Citar

1.
Hertz E, Turra BO, Bonotto NC de A, Trombini F dos S, Zimmermann JAB, Teixeira CF, Azzolin VF, Jung IE da C, Cruz IBM da, Barbisan F. Paclitaxel Modula a Proliferação e a Diferenciação de Células THP-1 Expostas ao Vírus SARS-CoV-2 Inativado. Rev. Bras. Cancerol. [Internet]. 15º de maio de 2025 [citado 6º de dezembro de 2025];71(2):e-265107. Disponível em: https://rbc.inca.gov.br/index.php/revista/article/view/5107

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ARTIGO ORIGINAL