Anti-tumor effect of Fasudil, a ROCK inhibitor, on gastric cancer in mice
Keywords:
apoptosis, Fasudil, gastric cancer, inflammation mediators, oxidative stressAbstract
Gastric cancer remains one of the most common malignant tumors and a leading cause of death. However, there are few reports about the anti-tumor effect of Fasudil (Fas) on the stomach. Establishment of nude mice model of gastric cancer to evaluate the anti-tumor effect of Fas. The mice in each group were weighed every week. Serum and tumor tissue cytokines are detected by commercial kits. Serum and tumor tissue superoxide dismutase and malondialdehyde were detected by commercial kits. Histopathological changes in the tumor were detected by HE staining. Expression of ROS/ TXNIP/NLRP3/Caspase-1 pathway in tumor tissues was detected by Western blot. Our results showed that Fas increased and decreased the body weight of tumor mice, increased serum and tumor tissue cytokines contents of tumor mice, increased serum and tumor tissue oxidative stress of tumor mice, and increased Bax, Caspase-3, Caspase-9 protein expression, reduced Bcl-2 protein expression, also regulated ROS/TXNIP/NLRP3/Caspase-1 pathway expression. Our experiments show that Fas has a significant anti-gastric cancer effect, and its mechanism is related to the regulation of oxidative stress, inflammation and apoptosis in vivo.
Downloads
References
Broz, P., & Dixit, V. M. (2016). Inflammasomes: mechanism of assembly, regulation and signalling. Nature Reviews Immunology, 16(7), 407-420.
Deng, L., Li, G., Li, R., Liu, Q., He, Q., & Zhang, J. (2010). Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo. Cancer biology & therapy, 9(11), 875-884.
Doonan, F., & Cotter, T. G. (2008). Morphological assessment of apoptosis. Methods, 44(3), 200-204. https://doi.org/10.1016/j.ymeth.2007.11.006
Freeman, S., Brough, D., & El-Sharkawy, L. (2020). Inhibiting the NLRP3 Inflammasome. Molecules, 25(5533).
Guerra, F. S., Oliveira, R. G. D., Fraga, C. A. M., Mermelstein, C. D. S., & Fernandes, P. D. (2017). ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells. Scientific reports, 7(1), 13723.
Jiang, D., Chen, S., Sun, R., Zhang, X., & Wang, D. (2018). The NLRP3 inflammasome: role in metabolic disorders and regulation by metabolic pathways. Cancer letters, 419, 8-19. https://doi.org/10.1016/j.canlet.2018.01.034
Lv, Z., Ding, Y., Cao, W., Wang, S., & Gao, K. (2022). Role of RHO family interacting cell polarization regulators (RIPORs) in health and disease: Recent advances and prospects. International Journal of Biological Sciences, 18(2), 800.
Macias-Alvia, A. M., Zambrano-Santos, R. O., Zambrano-Ubillus, R. P., & Ubillús-Saltos, S. (2022). Self-care in primary health care in the nursing career. International Journal of Health Sciences, 6(3), 1671–1684. https://doi.org/10.53730/ijhs.v6n3.13694
Pachathundikandi, S. K., & Backert, S. (2018). Helicobacter pylori controls NLRP3 expression by regulating hsa-miR-223-3p and IL-10 in cultured and primary human immune cells. Innate immunity, 24(1), 11-23.
Ravizza, T., Balosso, S., & Vezzani, A. (2011). Inflammation and prevention of epileptogenesis. Neuroscience letters, 497(3), 223-230. https://doi.org/10.1016/j.neulet.2011.02.040
Russo, A., Terrasi, M., Agnese, V., Santini, D., & Bazan, V. (2006). Apoptosis: a relevant tool for anticancer therapy. Annals of Oncology, 17, vii115-vii123. https://doi.org/10.1093/annonc/mdl963
Saif, M. W., Makrilia, N., Zalonis, A., Merikas, M., & Syrigos, K. (2010). Gastric cancer in the elderly: an overview. European Journal of Surgical Oncology (EJSO), 36(8), 709-717. https://doi.org/10.1016/j.ejso.2010.05.023
Sarkar, D., & Fisher, P. B. (2006). Molecular mechanisms of aging-associated inflammation. Cancer letters, 236(1), 13-23. https://doi.org/10.1016/j.canlet.2005.04.009
Sies, H. (2018). On the history of oxidative stress: Concept and some aspects of current development. Current Opinion in Toxicology, 7, 122-126. https://doi.org/10.1016/j.cotox.2018.01.002
Smyth, E. C., Nilsson, M., Grabsch, H. I., van Grieken, N. C., & Lordick, F. (2020). Gastric cancer. The Lancet, 396(10251), 635-648.
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
Tanaka, K., Minami, H., Kota, M., Kuwamura, K., & Kohmura, E. (2005). Treatment of cerebral vasospasm with intra-arterial fasudil hydrochloride. Neurosurgery, 56(2), 214-223.
Thrift, A. P., & El-Serag, H. B. (2020). Burden of gastric cancer. Clinical Gastroenterology and Hepatology, 18(3), 534-542. https://doi.org/10.1016/j.cgh.2019.07.045
Wang, H., Luo, Q., Feng, X., Zhang, R., Li, J., & Chen, F. (2018). NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma. BMC cancer, 18, 1-10.
Wang, N., Guan, P., Zhang, J. P., Chang, Y. Z., Gu, L. J., Hao, F. K., ... & Chu, L. (2011). Preventive effects of fasudil on adriamycin-induced cardiomyopathy: possible involvement of inhibition of RhoA/ROCK pathway. Food and chemical toxicology, 49(11), 2975-2982. https://doi.org/10.1016/j.fct.2011.06.080
Wang, Q., Song, L. J., Ding, Z. B., Chai, Z., Yu, J. Z., Xiao, B. G., & Ma, C. G. (2022). Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases. Neural regeneration research, 17(12), 2623.
Yamashita, K., Kotani, Y., Nakajima, Y., Shimazawa, M., Yoshimura, S. I., Nakashima, S., ... & Hara, H. (2007). Fasudil, a Rho kinase (ROCK) inhibitor, protects against ischemic neuronal damage in vitro and in vivo by acting directly on neurons. Brain research, 1154, 215-224. https://doi.org/10.1016/j.brainres.2007.04.013
Zhang, X., & Wu, N. (2018). Fasudil inhibits proliferation and migration of Hep-2 laryngeal carcinoma cells. Drug design, development and therapy, 373-381.
Published
How to Cite
Issue
Section
Copyright (c) 2023 International journal of health sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles published in the International Journal of Health Sciences (IJHS) are available under Creative Commons Attribution Non-Commercial No Derivatives Licence (CC BY-NC-ND 4.0). Authors retain copyright in their work and grant IJHS right of first publication under CC BY-NC-ND 4.0. Users have the right to read, download, copy, distribute, print, search, or link to the full texts of articles in this journal, and to use them for any other lawful purpose.
Articles published in IJHS can be copied, communicated and shared in their published form for non-commercial purposes provided full attribution is given to the author and the journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
This copyright notice applies to articles published in IJHS volumes 4 onwards. Please read about the copyright notices for previous volumes under Journal History.