AZT and emodin exhibit synergistic growth-inhibitory effects on K562/ADM cells by inducing S phase cell cycle arrest and suppressing MDR1 mRNA/p-gp protein expression.

Pharmaceutical biology

PubMedID: 24004004

Chen P, Liu Y, Sun Y, Chen C, Qi Y, Zhang Y. AZT and emodin exhibit synergistic growth-inhibitory effects on K562/ADM cells by inducing S phase cell cycle arrest and suppressing MDR1 mRNA/p-gp protein expression. Pharm Biol. 2013;.
Abstract Context: Previous studies have demonstrated that both 3'-azido-3'-deoxythymidine (AZT) and emodin, a traditional chemotherapy agent, can inhibit the growth of many types of cancer cells. Objective: This study aimed to evaluate the effect of AZT and emodin on adriamycin-resistant human chronic myelogenous leukemia (K562/ADM) cells, determine the expression of multidrug resistance 1 (MDR1) mRNA/p-glycoprotein (p-gp) protein, a protein known to induce resistance to anticancer agents, and to elucidate the underlying molecular mechanisms. Materials and methods: K562/ADM cells were treated with AZT (10-160?µM) or emodin (5-80?µM) for 24,?48 and 72?h and cell viability was measured using the MTT assay. The effect of AZT (16.5, 33 and 66?µM) and emodin (6.1,?17.6 and 33.2?µM) on K562/ADM cell cycle distribution was determined by flow cytometry, and MDR1 mRNA/p-gp protein expression was determined by real time RT-PCR and western blotting. Results: The growth suppression of emodin was dramatically enhanced by AZT in K562/ADM cells. The IC50 of AZT and emodin was lower than that of emodin alone. All examined combinations of AZT and emodin yielded a synergetic effect (CI?