HA1077 inibe a proliferação celular em carcinoma de células escamosas oral in vitro

Autores

DOI:

https://doi.org/10.33448/rsd-v11i3.26730

Palavras-chave:

Proliferação celular; HA-1077; Carcinoma de células escamosas oral; ROCKs; SCC-4; Y-27632.

Resumo

Uma forma de tentar controlar o carcinoma de células escamosas oral é investir em novas terapias voltadas para a biologia molecular dos receptores e suas vias de sinalização intracelular. Este estudo teve como objetivo avaliar o efeito do LY2109761 (um inibidor dos receptores TGF-β) na migração celular no carcinoma epidermóide oral in vitro. Citoesqueleto de actina de controle de células SCC-4 e LY2109761 (1, 5 e 10 μM) tratado em Matrigel tridimensional foram analisados ​​usando microscopia confocal a laser. Controle e células tratadas com LY2109761 (1, 5 e 10 μM) que migraram através da membrana de ensaios de migração de células tridimensionais foram contadas, a significância foi p <0,05. Células controle foram observadas com citoplasma volumoso, córtex celular preservado e citoesqueleto de actina bem desenvolvido com filamentos de actina bem distribuídos. Independentemente da concentração, as células tratadas apresentaram: morfologia arredondada e tamanho pequeno, citoplasma escasso, F-actina cortical menos clara que as células de controle e rompimento dos filamentos de actina. As células migratórias foram inibidas pelo tratamento com LY2109761 [F (3, 11) = 3742, p <0,0001], de uma forma dependente da dose. Esses resultados sugerem que o LY2109761 exerce um efeito inibitório sobre o citoesqueleto de actina e a migração celular nas células SCC-4, portanto, é uma opção terapêutica promissora para o carcinoma de células escamosas oral.

Referências

Abe, H., Kamai, T., Hayashi, K., Anzai, N., Shirataki, H., Mizuno, T., & Yoshida, K. (2014). The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer, 14, 412. https://doi.org/10.1186/1471-2407-14-412

Abraham, M. T., Kuriakose, M. A., Sacks, P. G., Yee, H., Chiriboga, L., Bearer, E. L., & Delacure, M. D. (2001). Motility-related proteins as markers for head and neck squamous cell cancer. Laryngoscope, 111(7), 1285-1289. https://doi.org/10.1097/00005537-200107000-00027

Amano, M., Nakayama, M., & Kaibuchi, K. (2010). Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken), 67(9), 545-554. https://doi.org/10.1002/cm.20472

Amaya, C. N., Mitchell, D. C., & Bryan, B. A. (2017). Rho kinase proteins display aberrant upregulation in vascular tumors and contribute to vascular tumor growth. BMC Cancer, 17(1), 485. https://doi.org/10.1186/s12885-017-3470-7

Bora, I., & Shrivastava, N. (2017). ABCs of RhoGTPases indicating potential role as oncotargets. J Cancer Res Ther, 13(1), 2-8. https://doi.org/10.4103/0973-1482.204878

Breitenlechner, C., Gassel, M., Hidaka, H., Kinzel, V., Huber, R., Engh, R. A., & Bossemeyer, D. (2003). Protein kinase A in complex with Rho-kinase inhibitors Y-27632, Fasudil, and H-1152P: structural basis of selectivity. Structure, 11(12), 1595-1607.

Chiou, S. H., Yu, C. C., Huang, C. Y., Lin, S. C., Liu, C. J., Tsai, T. H., & Lo, J. F. (2008). Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res, 14(13), 4085-4095. https://doi.org/10.1158/1078-0432.CCR-07-4404

Coleman, M. L., Marshall, C. J., & Olson, M. F. (2004). RAS and RHO GTPases in G1-phase cell-cycle regulation. Nat Rev Mol Cell Biol, 5(5), 355-366. https://doi.org/10.1038/nrm1365

David, M., Petit, D., & Bertoglio, J. (2012). Cell cycle regulation of Rho signaling pathways. Cell Cycle, 11(16), 3003-3010. https://doi.org/10.4161/cc.21088

Defert, O., & Boland, S. (2017). Rho kinase inhibitors: a patent review (2014 - 2016). Expert Opin Ther Pat, 27(4), 507-515. https://doi.org/10.1080/13543776.2017.1272579

Demoulin, J. B., & Essaghir, A. (2014). PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev, 25(3):273-83. https://doi.org/10.1016/j.cytogfr.2014.03.003

Evan, G. I., & Vousden, K. H. (2001). Proliferation, cell cycle and apoptosis in cancer. Nature, 411(6835), 342-348. https://doi.org/10.1038/35077213

Glazer, C. A., Chang, S. S., Ha, P. K., & Califano, J. A. (2009). Applying the molecular biology and epigenetics of head and neck cancer in everyday clinical practice. Oral Oncol, 45(4-5), 440-446. https://doi.org/10.1016/j.oraloncology.2008.05.013

Gómez del Pulgar, T., Benitah, S. A., Valerón, P. F., Espina, C., & Lacal, J. C. (2005). Rho GTPase expression in tumourigenesis: evidence for a significant link. Bioessays, 27(6), 602-613. https://doi.org/10.1002/bies.20238

Hinsenkamp, I., Schulz, S., Roscher, M., Suhr, A. M., Meyer, B., Munteanu, B., & Burgermeister, E. (2016). Inhibition of Rho-Associated Kinase 1/2 Attenuates Tumor Growth in Murine Gastric Cancer. Neoplasia, 18(8), 500-511. https://doi.org/10.1016/j.neo.2016.07.002

Ishizaki, T., Uehata, M., Tamechika, I., Keel, J., Nonomura, K., Maekawa, M., & Narumiya, S. (2000). Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol, 57(5), 976-983.

Jiang, L., Wen, J., & Luo, W. (2015). Rho‑associated kinase inhibitor, Y‑27632, inhibits the invasion and proliferation of T24 and 5367 bladder cancer cells. Mol Med Rep, 12(5), 7526-7530. https://doi.org/10.3892/mmr.2015.4404

Johan, M. Z., & Samuel, M. S. (2019). Rho-ROCK signaling regulates tumor-microenvironment interactions. Biochem Soc Trans, 47(1), 101-108. https://doi.org/10.1042/BST20180334

Kleer, C. G., Teknos, T. N., Islam, M., Marcus, B., Lee, J. S., Pan, Q., & Merajver, S. D. (2006). RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck. Clin Cancer Res, 12(15), 4485-4490. https://doi.org/10.1158/1078-0432.ccr-06-0376

Kümper, S., Mardakheh, F. K., McCarthy, A., Yeo, M., Stamp, G. W., Paul, A., Marshall, C. J. (2016). Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis. Elife, 5, e12994. https://doi.org/10.7554/eLife.12203

Lin, X., Khalid, S., Qureshi, M. Z., Attar, R., Yaylim, I., Ucak, I., & Ismail, M. (2016). VEGF mediated signaling in oral cancer. Cell Mol Biol (Noisy-le-grand), 62(14), 64-68. https://doi.org/10.14715/cmb/ 2016.62.14.11

Liu, B. L., Sun, K. X., Zong, Z. H., Chen, S., & Zhao, Y. (2016). MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC). Oncotarget, 7(6), 6649-6664. https://doi.org/10.18632/oncotarget.6544

Massano, J., Regateiro, F. S., Januário, G., & Ferreira, A. (2006). Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 102(1), 67-76. https://doi.org/10.1016/j.tripleo.2005.07.038

Moreira Carboni, S. e. S., Rodrigues Lima, N. A., Pinheiro, N. M., Tavares-Murta, B. M., & Crema, V. O. (2015). HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma. Anticancer Drugs, 26(9), 923-930. https://doi.org/10.1097/CAD.0000000000000267

Qiu, M. K., Wang, S. Q., Pan, C., Wang, Y., Quan, Z. W., Liu, Y. B., & Ou, J. M. (2017). ROCK inhibition as a potential therapeutic target involved in apoptosis in hemangioma. Oncol Rep, 37(5), 2987-2993. https://doi.org/10.3892/or.2017.5515

Pereira, A. S. et al. (2018). Metodologia da pesquisa cientifica. UFSM. https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1.

Ragin, C., Liu, J. C., Jones, G., Shoyele, O., Sowunmi, B., Kennett, R., & Taioli, E. (2016). Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients. Carcinogenesis, 38(2):218-229. https://doi.org/10.1093/carcin/bgw203

Steeg, P. S. (2016). Targeting metastasis. Nat Rev Cancer, 16(4), 201-218. https://doi.org/10.1038/nrc.2016.25

Stucky, A., Sedghizadeh, P. P., Mahabady, S., Chen, X., Zhang, C., Zhang, G., & Zhong, J. F. (2017). Single-cell genomic analysis of head and neck squamous cell carcinoma. Oncotarget, 8(42):73208-73218. https://doi.org/10.18632/oncotarget.18021

Thompson, J. M., Nguyen, Q. H., Singh, M., Pavesic, M. W., Nesterenko, I., Nelson, L. J., & Razorenova, O. V. (2017). Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma. Oncogene, 36(8), 1080-1089. https://doi.org/10.1038/onc.2016.272

Travassos, D. C., Fernandes, D., Massucato, E. M. S., Navarro, C. M., & Bufalino, A. (2017). Squamous cell carcinoma antigen as a prognostic marker and its correlation with clinicopathological features in head and neck squamous cell carcinoma: Systematic review and meta-analysis. J Oral Pathol Med, 47(1):3-10. https://doi.org/10.1111/jop.12600

Vega, F. M., & Ridley, A. J. (2008). Rho GTPases in cancer cell biology. FEBS Lett, 582(14), 2093-2101. https://doi.org/10.1016/j.febslet.2008.04.039

Wang, Z. M., Yang, D. S., Liu, J., Liu, H. B., Ye, M., & Zhang, Y. F. (2016). ROCK inhibitor Y-27632 inhibits the growth, migration, and invasion of Tca8113 and CAL-27 cells in tongue squamous cell carcinoma. Tumour Biol, 37(3), 3757-3764. https://doi.org/10.1007/s13277-015-4115-6

Wei, L., Surma, M., Shi, S., Lambert-Cheatham, N., & Shi, J. (2016). Novel Insights into the Roles of Rho Kinase in Cancer. Arch Immunol Ther Exp (Warsz), 64(4), 259-278. https://doi.org/10.1007/s00005-015-0382-6

Xu, X. D., Shen, H. B., Zhu, L., Lu, J. Q., Zhang, L., Luo, Z. Y., & Wu, Y. Q. (2017). Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression. Onco Targets Ther, 10, 1827-1834. https://doi.org/10.2147/OTT.S93164

Yang, X., Di, J., Zhang, Y., Zhang, S., Lu, J., Liu, J., & Shi, W. (2012). The Rho-kinase inhibitor inhibits proliferation and metastasis of small cell lung cancer. Biomed Pharmacother, 66(3), 221-227. https://doi.org/10.1016/j.biopha.2011.11.011

Zhang, J., He, X., Ma, Y., Liu, Y., Shi, H., Guo, W., & Liu, L. (2015). Overexpression of ROCK1 and ROCK2 inhibits human laryngeal squamous cell carcinoma. Int J Clin Exp Pathol, 8(1), 244-251.

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26/02/2022

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BORGES, G. H.; CARBONI, S. de S. C. M. .; CARNEIRO, A. C. D. M. .; HISS, L. S. .; SILVEIRA, I. C. da; CREMA, V. O. HA1077 inibe a proliferação celular em carcinoma de células escamosas oral in vitro. Research, Society and Development, [S. l.], v. 11, n. 3, p. e36611326730, 2022. DOI: 10.33448/rsd-v11i3.26730. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/26730. Acesso em: 26 nov. 2024.

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