The experimental research of dexamethasone reducing paclitaxel chemotherapy on lung cancer cells / 中国药理学通报

ABSTRACT

Aim: To investigate the effect of dexamethasone on paclitaxel chemotherapy, when given before chemotherapy. Methods: MTT method was used to investigate the effects of paclitaxel at different concentrations and dexamethasone (10 μ, mol · L-1) combined with paclitaxel at indicate dosages on the cell viability of lung cancer cells A549 and Calu-1. The cell cycle was detected by flow cytometry. The effect of dexamethasone on protein expression of glucocorticoid receptor (GR), P-glycoprotein (P-gP) and multidrug resistance protein-1 (MRP-1) expression were detected by Western blot. The effect of dexamethasone on lung cancer resistance of paclitaxel xenografts in nude mice was studied as well. Results paclitaxel at indicate dosages with dexamethasone (10 μmol · L-1) showed significantly increased IC50 value (A549: from 0.58 to 1.35 μmol · L-1; Calu-1 from 1. 10 to 2. 10 μmol · L-1). Dexamethasone activated GR, increased GR expression, and up-regulated the expression of P-gP and MRP-1. Dexamethasone combined with paclitaxel significantly decreased the antitumor effect of paclitaxel on nude mice transplanted tumor. Conclusions Giving dexamethasone before chemotherapy may cause resistance to cancer cells and reduce the effect of paclitaxel chemotherapy.