Abstract
The mammalian target of rapamycin (mTOR) regulates the motility and invasion of cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition. In the present study, the anti-metastatic effect of cardamonin and its underlying molecule mechanisms were investigated on the highly metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and migration of LLC cells were measured by MTT, transwell and wound healing assays, respectively. The expression and activation of mTOR- and adhesion-related proteins were assessed by Western blotting. The in vivo effect of cardamonin on the metastasis of the LLC cells was investigated by a mouse model. Treated with cardamonin, the proliferation, invasion and migration of LLC cells were significantly inhibited. The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased. In addition, cardamonin inhibited the activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1). Furthermore, the tumor growth and its lung metastasis were inhibited by cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.
Highlights
Metastasis is the primary cause of death in most cancer patients
The Lewis lung carcinoma (LLC) cells were exposed to different concentrations of cardamonin for 48 h in MTT assay
The inhibitory effect of cardamonin on the ability of LLC cells to invade a reconstituted extracellular matrix was assessed by transwell chamber
Summary
Metastasis is the primary cause of death in most cancer patients. The process of metastasis consists of a series of sequential, interrelated steps. Tumor cells detach from the primary tumor is the first step of metastasis [1]. It maintains the cell-to-cell adhesion and decreases the separation of cancer cells from cancer tissues. The down-regulation of E-cadherin is a sign of poor prognosis, correlating with invasion and metastasis in multiple carcinomas [2, 3]. The deficiency of E-cadherin is one of the earliest steps in the epithelial-mesenchymal transition (EMT). It binds to the 5’-CACCTG-3’ sequence of E-cadherin promoter and represses the transcription of E-cadherin. Snail induces EMT by suppressing the adhesion
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