Reverse Effect of Interferon-α Combined with All-Trans Retinoic Acid on Multidrug Resistance of Human Leukemic Cell Line K562/ADM / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of interferon-α(IFN-α) and all-trans retinoic acid(ATRA) on multidrug resistance reversal effect and mechanism of human leukemia K562/ADM cells. METHODS: The cytotoxicity and reversal times of IFN-α and ATRA were detected by CCK-8 method. Apoptosis rate and cell cycle were detected by flow cytometry. PI3K, Akt and Bad mRNA were detected by RT-PCR method. Western blot method was used to detect the expression of PI3K, AKt, P-AKt and Bad protein.RESULTS: The drug resistance of K562/ADM cells to adriamycin(ADM) was 54 times. ADM, respectively, with IFN-α, ATRA or combined application, the drug resistance of K562/ADM cells to ADM was 1.24, 2.34 and 8.14, respectively. The apoptosis rate of K562/ADM cells was significantly increased by using ADM 4 mg·L-1alone or in combination with IFN-α 2.5×106 U·L-1, ATRA 7.5 μmol·L-1, and the cell cycle was blocked in G0/G1 phase. PI3K mRNA and protein expression were significantly lowered, Akt mRNA and protein has no obvious change, Bad mRNA and protein expression are raised, phosphorylated Akt protein expression decreased, the expression is more obvious when the two drug combination. CONCLUSION: IFN-α and ATRA can reverse the multidrug resistance of K562/ADM cells, its mechanism may be the inhibition of the PI3K/Akt pathway.