Cardamonin inhibits the expression of P-glycoprotein and enhances the anti-proliferation of paclitaxel on SKOV3-Taxol cells

AbstractPaclitaxel is widely used in the first-line treatment of ovarian cancer. Nevertheless, the development of acquired resistance to paclitaxel is a major obstacle for the therapy in clinic. Cardamonin is a novel anticancer chalcone which exhibits a wide range of pharmacological activities. However, the effect of cardamonin on paclitaxel-resistant ovarian cancer cells and its underlying molecular mechanisms are unknown. Here, we revealed whether cardamonin had a resensitivity for paclitaxel and furtherly explored the underlying mechanisms on SKOV3-Taxol cells. Our results showed that cardamonin combined with paclitaxel had a synergistic effect of anti-proliferation in SKOV3-Taxol cells, and CI was less than one. Cells apoptosis and G2/M phase arrest were enhanced by cardamonin with paclitaxel in a concentration-dependent way on SKOV3-Taxol cells (P <  0.05). Cardamonin significantly increased drug accumulation in SKOV3-Taxol cells (P <  0.05). Similar to verapamil, cardamonin decreasedMDR1 mRNA and P-gp expression (P <  0.05). Cardamonin restrained NF-κB activation in SKOV3-Taxol cells (P <  0.05). Inhibitory effect of P-gp and NF-κB p65 (nuclear protein) expression was enhanced by cardamonin combined with PDTC, a NF-κB inhibitor. Cardamonin significantly inhibited the upregulation of NF-κB p65 (nuclear protein) and P-gp expression induced by TNF-α (P <  0.05). Taken together, cardamonin enhanced the effect of paclitaxel on inhibiti...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research