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.

No abstract

The mammalian target of rapamycin is critical in hypoxia-triggered angiogenesis. Cardamonin inhibits proliferation of various cancer cells through suppressing the mammalian target of rapamycin. In this study, the antiangiogenic effect of cardamonin on CoCl2-mimicked hypoxic SKOV3 cells was investigated. Cardamonin exhibited an antiproliferative effect on normal and CoCl2-mimicked hypoxic SKOV3 cells. Messenger RNA expression of vascular endothelial growth factor was inhibited with cardamonin and rapamycin in SKOV3 cells under both conditions. However, cardamonin had little effect on the messenger RNA expression of hypoxia-inducible factor-α. Cardamonin inhibited the protein expression of hypoxia-inducible factor-1α, hypoxia inducible factor-2α, vascular endothelial growth factor, and the phosphorylation of mammalian target of rapamycin and ribosomal S6 kinase 1. Furthermore, angiogenesis induced by a medium of SKOV3 cells was reduced by cardamonin in a chicken embryo allantois membrane model. These findings suggest that cardamonin inhibits protein expression of hypoxia-inducible factor-α, and vascular endothelial growth factor, which was induced by CoCl2-mimicked hypoxia and this effect partially correlates with the mammalian target of rapamycin inhibition. Cardamonin might be a potential angiogenesis inhibitor for ovarian cancer therapy.

Advanced NSCLC patients with AA genotype of GSTP1 would obtain better curative effect followed with more risk of anemia when treated by cisplatin-based chemotherapy. ATP7A C2299G does not impact the efficacy and toxicity of cisplatin-based chemotherapy. XRCC1 1196A allele could predict the incidence of lymphopenia and diarrhea.

Abstract. The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic target in various cancer cells. mTOR activation decreases the sensitivity of ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various cancer cells by mTOR suppression. The present study examined whether cardamonin combined with cisplatin is efficacious for the anti-proliferation of ovarian cancer cells. The anti-proliferative effect was determined by MTT and cell cycle assays. Activation of the mTOR signal pathway and the expression of anti-apoptotic proteins were evaluated by western blot analysis. Cardamonin significantly enhanced the effects of cisplatin on cell proliferation and cell cycle progression. The expression of B cell lymphoma-2, X-linked inhibitor of apoptosis protein and Survivin was significantly decreased following combination treatment. Furthermore, the activation of mTOR and its downstream 70 kDa ribosomal protein S6 kinase was inhibited by cardamonin. These results demonstrated that the combinatorial effects of cardamonin and cisplatin on anti-proliferation were enhanced by suppressing the expression of anti-apoptotic proteins and activation of mTOR in ovarian cancer cells.