Abstract
Thymoquinone, isolated from the seeds of Nigellasativa, 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.
Highlights
Renal cell carcinoma (RCC) is the most common type of kidney cancer worldwide [1]
In order to confirm the effect of TQ on RCC cell migration and invasion, it was essential to determine the concentration‐dependent effect of TQ on cell viability
TQ was found to inhibit the metastasis of melanoma through the downregulation of NLRP3 (NACHT, LRR and pyrin domain‐containing protein 3) inflammasome [19]
Summary
Despite the improvement of diagnostic techniques and therapeutic treatments, the majority of patients with RCC are diagnosed at an advanced stage or have already presented with metastasis. It is reported that in 30% of patients with RCC, metastatic lesions have already developed at the stage of diagnosis [2]. Numerous studies have reported that TQ has broad pharmacological effects. TQ is reported to have antioxidant effects in activated BV‐2 murine microglial cells [5]. Previous studies revealed that TQ has KOU et al: THYMOQUINONE INHIBITS METASTASIS IN RENAL CELL CARCINOMA antitumor activities such as suppression of proliferation, induction of apoptosis, inhibition of metastasis and enhancement of chemosensitivity [6,7,8,9]. Few studies have been performed about the effect of TQ on migration and invasion in RCC
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