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.

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 < 1). Furthermore, AZT and emodin altered the cell cycle distribution and led to an accumulation of cells in S phase. Meanwhile, the expression of MDR1 mRNA/p-gp protein was markedly decreased.

DISCUSSION AND CONCLUSION

These results show a synergistic growth-inhibitory effect of AZT and emodin in K562/ADM cells, which is achieved through S phase arrest. MDR1 might ultimately be responsible for these phenomena.