Thymoquinone inhibits metastatic phenotype and epithelial‑mesenchymal transition in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway
| Autor: | Qingshan Kou, Borui Sun, Jianpeng Li, Jing Zhang, Yang Yang, Jinsong Zhou, Bo Ma, Bo Kou, Wei Liu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Cell Apoptosis Vimentin AMP-Activated Protein Kinases Protein Serine-Threonine Kinases 03 medical and health sciences chemistry.chemical_compound AMP-Activated Protein Kinase Kinases Cell Movement Benzoquinones Biomarkers Tumor Tumor Cells Cultured medicine Humans Epithelial–mesenchymal transition Phosphorylation Protein kinase A Carcinoma Renal Cell Thymoquinone Cell Proliferation biology Oncogene AMPK General Medicine Cell cycle Kidney Neoplasms Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology chemistry biology.protein Cancer research |
| Zdroj: | Oncology Reports. |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2018.6519 |
| Popis: | Thymoquinone, isolated from the seeds of Nigella sativa, has exhibited antitumor properties in a variety of cancer types. However, few studies have investigated the effect of thymoquinone (TQ) on migration and invasion in renal cell carcinoma (RCC). In the present study, our results confirmed that TQ significantly inhibited the migration and invasion of the human RCC 769‑P and 786‑O cell lines, as demonstrated by wound healing and Transwell assays. Additionally, TQ upregulated the expression of E‑cadherin and downregulated the expression of Snail, ZEB1 and vimentin at the mRNA and protein levels in a concentration‑dependent manner. Subsequently, the phosphorylation levels of liver kinase B1 (LKB1) and AMP‑activated protein kinase (AMPK) were increased upon TQ treatment. To further validate the role of LKB1/AMPK signaling, we revealed that TQ‑mediated increase of E‑cadherin level and reduction of Snail level could be further enhanced by LKB1 overexpression. Furthermore, co‑treatment with the AMPK inhibitor Compound C attenuated the anti‑metastatic effect of TQ on RCC and partially abrogated the high expression of E‑cadherin and the low expression of Snail mediated by TQ. In contrast, the AMPK activator AICAR demonstrated the opposite effect. Collectively, the present study revealed that TQ could markedly suppress the metastatic phenotype and reverse the epithelial‑mesenchymal transition in RCC by regulating the LKB1/AMPK signaling pathway, indicating that TQ may be a potential therapeutic candidate against RCC. |
| Databáze: | OpenAIRE |
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