OBJECTIVETo investigate the molecular mechanism of arsenic trioxide(ATO) inhibiting K562 cell proliferation, and explore the new targets for treating chronic myeloid leukemia(CML).

METHODShuman CML cell line K562 cells were cultured in vitro, and were treated with different concentrations of ATO; MTT was used to detect the cell proliferation; flow cytometry(FCM) was used to determine cell apoptosis, cell cycle and the expression of CD44; Transcriptional levels of β-catenin and cyclin D1 were assayed by RT-PCR.

RESULTS2 µmol/L ATO could inhibit the cell proliferation obviously in a time-and-dose-dependent manner. With drug concentration increasing and time prolonging, the expression rate of CD44 was declined gradrually. FCM with AnnexinV/PI double staining showed that K562 cells were induced to apoptosis after exposure to 2.5-10 µmol/L ATO for 48 hours and in dose-dependent manner. Treating with different concentration ATO for 48 hours, cell ratio of G/Gphase increased and cell ratio in S phase decreased gradually. RT-PCR showed that the expression of β-catenin and CyclinD1 decreased with increasing of drug concentration.

CONCLUSIONATO in certain concentration range can inhibit K562 cell proliferation, and induce the cell apotosis, the mechanismin influencing the Wnt/β-catenin pathway may be the downregulation of CD44 expression, arresting K562 cells in G/Gphase, and affecting the gene transcription, thus inhibiting K562 cell proliferation.