Objective:To investigate the synergistic effects of carnosic acid(CA) with arsenic trioxide(As_2O_3) on proliferation and apoptosis in HL-60 human myeloid leukemia cells,and the major cellular signaling pathway involved in these effects.Methods:HL-60 cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide(MTT) analysis.Cell cycle distribution and apoptosis were monitored by flow cytometry.The activation of casepase-9,Bcl-2-associated agonist of cell death(BAD),p-BAD,p27,phosphatase and tensin homolog deleted on chromosome ten(PTEN),Akt,p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction(RT-PCR) analysis.Results:CA reduced HL-60 cell viability in a dose- and time-dependent manner,and induced G1 arrest and apoptosis.Moreover,CA upregulated PTEN expression,blocked the Akt signaling pathway,subsequently inhibited phosphorylation of BAD,reactivated caspase-9,and elevated levels of p27.CA also augmented these effects of As_2O_3.Conclusion:CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway. Objective: To investigate the synergistic effects of carnosic acid (CA) with arsenic trioxide (As_2O_3) on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects. Methods: HL-60 was measured by 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl- associated agonist of cell death (BAD), p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten (PTEN), Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, phosphorylation of BAD, reactivated caspase-9, and el evated levels of p27.CA also augmented these effects of As_2O_3.Conclusion: CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN / Akt signaling pathway.