HA1077 inhibe la proliferación celular en el carcinoma oral de células escamosas in vitro

Autores/as

DOI:

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

Palabras clave:

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

Resumen

El carcinoma oral de células escamosas es una lesión maligna común. Las proteínas ROCKs están asociadas con la patogénesis y progresión de tumores humanos. Este estudio tuvo como objetivo evaluar el papel funcional de las ROCK en la regulación de la proliferación celular del carcinoma oral de células escamosas in vitro. Los ensayos de incorporación de BrdU y la inmunoexpresión de KI-67 se realizaron utilizando la línea celular SCC-4 de carcinoma de células escamosas orales. Células control y tratadas: HA-1077 (25, 50 y 100 μmol/l), 50 μmol HA-1077 y Y-27632 30 μmol/l, Y-27632 30 μmol/l se cultivaron durante 6 h. El número de células SCC-4 tratadas con: HA-1077 (25, 50 y 100 μmol/l), HA-1077 50 μmol/l y/o Y-27632 30 μmol/l fue significativamente menor que las células de control en el ensayo BrdU [F (5,17) = 443.818, p<0,0001] y en ensayo KI-67 [F = 192.595, df = 5,17; p<0,0001]. Los resultados obtenidos sugieren que las vías que evolucionan las proteínas ROCKs juegan un papel funcional importante en la regulación positiva de la proliferación celular en el carcinoma de células escamosas oral.

Citas

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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Publicado

26/02/2022

Cómo citar

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 inhibe la proliferación celular en el carcinoma oral de células escamosas 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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