Zoledronic acid inhibits proliferation and induces apoptosis in U937 cells / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM:To study the antiproliferation and proapoptotic effects of zoledronic acid ( ZOL) on human a-cute myeloid leukemia cell line U937.METHODS:The viability of U937 cells was detected by CCK-8 assay.The cell cy-cle of the U937 cells was analyzed by flow cytometry with PI staining.Apoptotic rate was assessed by flow cytometry with Annexin V-PI and Hoechst 33342 staining.Mitochondrial membrane potential was detected by JC-1 assay.Methylcellulose was used to assess colony formation.The protein levels of p21, Bcl-2 and Bax were determined by Western blot.RE-SULTS:ZOL inhibited the viability of U937 cells.ZOL induced S-phase cell cycle arrest in the U937 cells.The results of flow cytometry analysis with Annexin V-PI and Hoechst 33342 staining showed that ZOL also induced apoptosis in a dose-and time-dependent manner.Mitochondrial membrane potential assay was also used to verify the apoptosis.The apoptotic rate was consistent with the reduction of mitochondrial membrane potential.Colony formation assay showed that ZOL signifi-cantly inhibited the colony formation capacity of the U937 cells.This was achieved by the induction of S-phase cell cycle arrest, and up-regulation of Bax and p21, and down-regulation of Bcl-2.CONCLUSION:ZOL inhibits cell proliferation by regulating the expression of cell cycle-related protein, and induces apoptosis via the mitochondrial apoptotic pathway.