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.
Oncology reports. 2018 Jun 25 [Epub ahead of print]
Bo Kou, Qingshan Kou, Bo Ma, Jing Zhang, Borui Sun, Yang Yang, Jianpeng Li, Jinsong Zhou, Wei Liu
Department of Cardiovascular Surgery, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Medical Center, The First People's Hospital of Xianyang, Xianyang, Shaanxi 712000, P.R. China., Department of Ophthalmology, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Gynaecology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710061, P.R. China., Department of Anesthesiology, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China., Department of Vascular Surgery, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.