Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways
| Autor: | Fan Zhao, Yi Wang, Zunhe Zhong, Jiangtao Zhan, Mianchuan Chen, Ruifa Han, Xianping Che |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cell signaling Article Subject Cell Survival MAP Kinase Signaling System TRPM Cation Channels Apoptosis Protein Serine-Threonine Kinases urologic and male genital diseases General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Cell Movement TRPM7 Annexin Cell Line Tumor medicine Animals Humans Protein kinase B Tumor Stem Cell Assay Cell Proliferation Bladder cancer General Immunology and Microbiology Chemistry General Medicine medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL 030104 developmental biology Urinary Bladder Neoplasms 030220 oncology & carcinogenesis Cancer research Medicine Female Signal transduction Diterpenes Kaurane Proto-Oncogene Proteins c-akt Research Article |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2021 (2021) |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2021/4340950 |
| Popis: | Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention. |
| Databáze: | OpenAIRE |
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